Ömer Hınç Yılmaz

Immunomodulation and Oxidative Stress in Denim Sandblasting Workers: Changes Caused by Silica Exposure

Abstract Workers in denim sandblasting are at a high risk of developing silicosis, an occupational lung disease caused by inhaling crystalline silica dust. The development and progress of silicosis is associated with the activation of the immune system and oxidative stress. In the former, interferon-gamma induces both neopterin release and the enzyme indoleamine [2, 3]-dioxygenase (IDO) in various cells. The determination of the kynurenine-to-tryptophan ratio and neopterin concentration has proven to be an efficient method to monitor the activation status of IDO and cellular immunity. The present study aimed to investigate whether occupational silica exposure leads to any alterations in neopterin levels, tryptophan degradation, and activities of superoxide dismutase (SOD) and catalase (CAT), agents in the antioxidant defense system. Fifty-five male denim sandblasting workers and twenty-two healthy men as controls were included. Mean neopterin and kynurenine levels, kynurenine-to-tryptophan ratio, and SOD activity were higher in subjects with silicosis compared to non-exposed controls (all, p<0.05). Neopterin levels and kynurenine-totryptophan ratios were positively correlated (p<0.05); however, no correlation was observed between length of employment and the measured parameters. Some of the measured parameters were significantly affected by the severity of the pathology. Our results suggest that silica exposure activates the cellular immune response. The increased neopterin levels and tryptophan degradation confirm the possibility of their use as an indicator of cellular immune response. Sažetak IMUNOMODULACIJA I OKSIDATIVNI STRES U RADNIKA U PJESKARENJU TRAPER PLATNA: PROMJENE UZROKOVANE IZLOŽENOSTI SILICI Radnici u pjeskarenju traper platna izloženi su visokom riziku od silikoze, profesionalne plućne bolesti uzrokovane udisanjem čestica silikatne prašine. Razvoj i progresija silikoze povezani su s aktivacijom imunosnog sustava i oksidativnim stresom. Pri aktivaciji imunosnoga sustava, interferon-gama potiče otpuštanje neopterina i enzima indoleamina [2, 3]-dioksigenaze (IDO) u različitim vrstama stanica. Određivanje omjera kinurenina i triptofana te koncentracije neopterina pokazale su se učinkovitim metodama praćenja aktivacijskoga statusa IDO-a i staničnog imuniteta. Ovaj rad istražuje uzrokuje li profesionalna izloženost silici promjene u razinama neopterina, degradaciji triptofana i aktivnosti superoksid dismutaze (SOD) i katalaze (CAT), agenata u antioksidativnom obrambenom sustavu. U istraživanju je sudjelovalo 55 muških radnika u pjeskarenju traper platna i 22 zdrava muškarca u kontrolnoj skupini. Srednje vrijednosti razina neopterina i kinurenina, omjera kinurenina i triptofana, te aktivnosti SOD-a bile su više u radnika oboljelih od silikoze nego u kontrolnoj skupini (p<0,05). Razina neopterina i omjer kinurenina i triptofana bile su u pozitivnoj korelaciji (p<0,05). Međutim, korelacija nije uočena između mjerenih vrijednosti i radnog staža. Neke od mjerenih vrijednosti bitno su ovisile o težini patologije. Dobiveni rezultati daju naslutiti da izloženost silici uzrokuje aktivaciju staničnog imunosnog odgovora. Povećane razine neopterina i degradacije triptofana potvrđuju mogućnost njihova korištenja kao pokazatelja staničnog imunosnog odgovora.

The compromise of dynamic disulfide/thiol homeostasis as a biomarker of oxidative stress in trichloroethylene exposure

In this study, we aimed to investigate disulfide/thiol homeostasis in trichloroethylene (TCE) exposure. The study was carried out in 30 nonsmoker TCE-exposed workers with a variety of occupations. Additionally, 30 healthy nonsmoker volunteers were recruited as the control group. TCE exposure was determined by measuring urinary trichloroacetic acid (TCA) concentration. Median urinary TCA levels of exposed workers (20.5 mg/L) were significantly higher than control subjects (5 mg/L). Thiol and disulfide concentrations were determined using a novel automated method. Disulfide/thiol ratio was significantly higher in the exposed group (p < 0.001). Thiol/disulfide homeostasis was found to be disturbed in TCE-exposed workers. We predict that in TCE-exposed workers this disturbance can be a therapeutic target, and the efficiency of the treatment can easily be monitored by the novel method we used.

Thiol/disulfide homeostasis in asphalt workers

ABSTRACT 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.

Lead exposure is related to impairment of aortic elasticity parameters.

Arterial hypertension is one of the physical complications of chronic lead exposure. Hypertension has effects on aortic elastic properties. The aim of this study was to evaluate the aortic elastic properties in workers occupationally exposed to lead. Forty‐one workers who were exposed to lead and 39 healthy controls were included in the study. All patients underwent transthoracic echocardiography for detecting aortic elastic parameters. There were no differences in baseline characteristics between the lead‐exposure group and controls. Aortic strain (9.4%±4.5% vs 12.4%±4.2%, P=.004) and aortic distensibility (0.45±0.21 cm2/dyn vs 0.55±0.20 cm2/dyn, P=.046) were decreased in patients with lead exposure compared with controls. There was a negative significant weak correlation between aortic strain and (r=−0.294, P=.008) lead levels. There was no significant correlation between aortic distensibility and any other echocardiographic parameters. This study suggests that chronic exposure to lead is related to impairment of aortic elasticity parameters.

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.

Iron overload and fragmented QRS in patients with Thalassemia major: Mechanisms, therapies, and new horizons.

We read with great interest the manuscript written by Bayar et al. (1) entitled “Assessment of the relationship between fragmented QRS and cardiac iron overload in patients with beta-thalassemia major,” published in the February 2015 issue of the Anatolian Journal of Cardiology. In that study, they investigated the relationship between fragmented QRS (fQRS), which is a marker of depolarization abnormality, and the cardiac T2 value in magnetic resonance imaging (MRI) is used as a screening tool to evaluate the cardiac iron load in patients with beta thalassemia major. In this study, significant correlations were found between the presence of fQRS and cardiac iron overload detected by cardiac MRI. Furthermore, the effects of various chelating agents on the cardiac iron overload and the presence of fQRS were also evaluated and remarkable results have been achieved; however, we think that there are some confusing points in this respect. Firstly, in univariate analysis, it was shown in Table 2 that deferoxamine or deferasirox users compared with non-users had a low incidence of cardiac involvement. It could be true for deferasirox (OR 0.38 and 0=0.021); however, it is not clear whether deferoxamine (OR 2.73 and p=0.015) was associated with cardiac involvement or not. Additionally, it was stated that in deferoxamine or deferasirox users, the cardiac iron overload was less than in non-users, and fQRS presence of these patients also were shown to be less in Tables 3 and 4. However, in deferoxamine users, both the cardiac iron overload and fQRS presence were observed more frequently. Another small detail about the results is that the age of the participants should be expressed as “mean” and not as “median.” FQRS represents a conduction delay from inhomogeneous activation of the ventricles due to a myocardial scar and is thought to be associated with ventricular tachyarrhythmias (2). Although this arrhythmic marker has long been evaluated mainly in ischemic etiologies, it has been frequently investigated in non-ischemic cardiac diseases, particularly in systemic diseases associated with cardiac involvement, such as sarcoidosis and rheumatoid arthritis (3, 4). Patchy-like inhomogeneous deposition, localized fibrous replacement, and oxidative mechanisms seem to be responsible for the electrical heterogeneity of the ventricular myocardium (5). Beyond this “iatrogenic iron exposure,” toxic heavy metal and their chelation therapies that may have similar effects on myocardium may be considered to be a promising research subject.

Occupational exposure to asphalt fume can cause oxidative DNA damage among road paving workers

OBJECTIVES We designed the present study to determine the effect of occupational exposure to asphalt fumes on oxidative status and DNA damage in road paving workers. METHODS Sixty road paving workers exposed to asphalt fumes and forty non-exposed control subjects were recruited. Occupational exposure to PAHs was assessed by urinary 1-hydroxypyrene (1-OHP) excretion. Serum thiol disulfide homeostasis (TDH), total oxidant status (TOS) and total antioxidant status (TAS) and urinary 8-hydro-deoxyguanosine (8-OH-dG) level were evaluated by automated colourimetric method. RESULTS The urinary concentrations of 1-OHP and 8-OH-dG were significantly higher in the exposed group than in the control group (P < 0.001). Disulfide/thiol ratio, TOS, and TAS were also significantly higher for the asphalt workers. A positive correlation existed between urinary 1-OHP and 8-OH-dG, TOS and TAS. CONCLUSION Study results indicate that exposure to PAHs induces oxidative stress and causes genotoxic effects in asphalt workers.

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

Abstract 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.

Assessment of renal functions with different glomerular filtration rate formulas in children with acute exposure of mercury

Abstract Objective: Our aim was to determine whether cystatin C level has a superiority to creatinine to assess kidney functions in rapid decreases of glomerular filtration rate due to acute mercury exposure in children. Eight different glomerular filtration rate calculation formulas which have been used creatinine and/or cystatin C were also compared. Methods: Serum urea, creatinine and cystatin C values of 39 mercury exposed children were measured. Glomerular filtration rates were calculated by eight different formulas. Patient group was divided into three subgroups according to mercury levels. Results: Cystatin C and mercury levels of the patients were found significantly different from control group (p<0.001). There was not a significant difference in creatinine and urea values between two groups (p=0.913, p=0.236). There was not a significant difference between patient and control groups in GFR calculations which have been used serum creatinine and height or which have been used urea additional to them (p=0.069, p=0.559, p=0.424, p=0.945, respectively), but there was a significant difference between patient and control groups in GFR calculations which have been used cystatin C only or creatinine, urea and height in addition to this (p<0.001, p<0.001, p=0.042, p<0.001, respectively). In sugroup analysis, cystatin C results and the results of three GFR calculations of four GFR calculations which were used cystatin C were found different in control group according to subgroups but there was not a difference between subgroups. Conclusion: Cystatin C level is a better indicator than creatinine to assess kidney functions in rapid decreases of glomerular filtration rate due to acute exposure of mercury. Formulas using cystatin C gave better results than formulas using creatinine and height in estimation of glomerular filtration rate. Özet Amac: Cocuklarda akut civa maruziyetine bağlı hızlı glomeruler fitrasyon hızı azalmalarında sistatin C duzeyinin bobrek fonksiyonlarını değerlendirme acısından kreatinine ustun olup olmadığını belirlemeyi amacladık. Ayrıca kreatinin ve/veya sistatin C kullanılan 8 ayrı glomerular filtrasyon hızı hesaplama formulunu birbiriyle karşılaştırdık. Metod: Civa maruziyeti yaşayan 39 cocuğun serum ure, kreatinin ve sistatin C duzeyleri olculdu. Glomerular filtrasyon hızı 8 farklı formulle hesaplandı. Hasta grubu civa seviyelerine gore uc subgruba bolundu. Bulgular: Hastaların sistatin C ve civa duzeyleri kontrol grubundan anlamlı olarak farklı bulundu (p<0.001). Kreatinin ve ure acısından iki grup arasında anlamlı bir fark bulunmadı (p=0.913, p=0.236). Serum kreatinini ve boy kullanılarak veya bunlara ilaveten ure değerleri kullanılarak yapılan GFR hesaplamalarında hasta ve kontrol grupları arasında anlamlı bir fark yokken (sırasıyla, p=0.069, p=0.559, p=0.424, p=0.945 ), yalnızca sistatin C veya buna ek olarak kreatinin, ure ve boyun kullanıldığı GFR hesaplamalarında hasta ve kontrol grupları arasında anlamlı bir fark vardı (sırasıyla, p<0.001, p<0.001, p=0.042, p<0.001). Subgrup analizinde sistatin C sonucları ile sistatin C kullanılarak hesaplanan dort GFR hesaplamasından uc tanesine ait sonuclar kontrol grubunda subgruplara gore farklı bulunurken subgruplar arasında farklı bulunmadı. Sonuç: Akut maruziyetlere bağlı hızlı glomeruler fitrasyon hızı azalmalarında sistatin C duzeyi bobrek fonksiyonlarını değerlendirme acısından kreatinine ustundur. Sistatin C kullanılarak oluşturulan formuller glomeruler filtrasyon hızını belirlemede kreatinin ve boy uzunluğu kullanılarak oluşturulan formullere kıyasla daha iyi sonuc vermektedir.

Additional diagnostic parameter for coronary artery disease during exercise test: heart rate recovery.

We read with great interest the manuscript written by Akyüz et al. (1), entitled “Heart rate recovery may predict the presence of coronary artery disease,” in the June issue of Anatolian Journal of Cardiology 2014;14:351-6. In that study, they investigated whether post-exercise first-minute abnormal heart rate recovery (HRR1) helps to predict the presence and severity of coronary artery disease (CAD) (1). They found that abnormal HRR, which was defined as ≤21 beats in the sitting position during the first minute of the recovery period, had moderate sensitivity and low specificity for predicting the presence of CAD. However, abnormal HRR was not predictive of the severity of CAD. HRR after graded exercise is one of the commonly used parameters to reflect autonomic activity. Abnormal HRR might be attributable to a defect in sympathetic withdrawal, parasympathetic reactivation, or both. Because these changes correlate with an increased risk of death, it has been hypothesized that an abnormal HRR would similarly predict increased mortality. Chaitman et al. (2) showed that the mechanism of increased mortality associated with abnormal HRR might be related more to autonomic dysfunction than to the presence or extent of CAD. On the other hand, Kizilbash et al. (3) suggested that blunted HRR was associated with several risk factors of CAD. In addition, Gera et al. (4) found that abnormal HRR was also associated with a high prevalence of CAD, left ventricular dysfunction, and composite high-risk myocardial perfusion imaging findings. In concordance with the basic findings of the study by Akyüz et al. (1), they also suggested that abnormal HRR alone, noted on stress testing, might warrant further evaluation for suspected CAD. When this relationship of abnormal HRR with CAD is taken in an opposite way, there are studies supporting this relationship. It has been shown that various programs that have been performed to control underlying CAD or rehabilitation of a CAD patient improve HRR. Tsai et al. (5) found that patients who were enrolled in a cardiac rehabilitation program after undergoing coronary artery bypass graft surgery had significantly higher HRR values compared to the control group. In conclusion, although HRR and CAD prediction are and will further be a topic of hot debate, such an index, which can very easily be obtained during exercise stress test, can be used as a diagnostic parameter, in addition to the more commonly used parameters, including ST-segment depression, typical chest pain, or hypotensive response.