Thromboangiitis Obliterans Biomarker Shifts in Different Acute Phase Stages: A Case Study.

Thromboangiitis obliterans (TAO) is a rare vasculopathy that is predominantly seen in young male smokers. Recently, new biomarkers have been shown to be useful in distinguishing TAO from acute phase TAO in an Asian study population. The present case study illustrates their application in a European patient during TAO exacerbation and their association with therapeutic performance.

Fibrinogen, Neutrophil-to-Lymphocyte Rate and Platelet-to-Neutrophil Rate as Novel Acute Phase Indicators in Patients with Thromboangiitis Obliterans.

BACKGROUND/OBJECTIVES: The acute exacerbations and progressive deterioration seen in thromboangiitis obliterans (TAO) have been related to poor clinical outcomes. Here, we have studied the association of laboratory biomarkers with the acute phase of TAO (AP-TAO). METHODS/RESULTS: We conducted a retrospective case-control study on 112 patients with TAO and 98 healthy controls; comparing the neutrophil-to-lymphocyte rate (NLR), lymphocyte-to-monocyte rate (LMR), platelet-to-neutrophil rate (PNR), fibrinogen (FIB), and apolipoprotein A-I (ApoA-I). Significantly higher NLR level, as well as lower LMR, PNR, and ApoA-I levels were observed in patients with TAO, particularly the acute phase. Significantly increased FIB was only observed in AP-TAO. A positive correlation was found between NLR and with C-reactive protein (CRP) in the acute phase (r = 0.817, P < 0.001). Moreover, NLR, PNR, and FIB levels of 3.38, 45.12, and 3.69 were shown to be the predictive cut-off values for the AP-TAO (sensitivity 72.5, 82,4, and 66,7%, specificity 92.2, 78.4, and 96.1%; area under the curve [AUC] 0.875, 0.855, and 0.872), respectively. The FIB level was independently associated with the AP-TAO (OR = 11.420, P = 0.007). CONCLUSIONS: NLR, PNR, and FIB may be useful markers for the identification of inflammation and the AP-TAO. FIB may be an independent risk factor for the acute phase.

D-dimer levels in patients with thromboangiitis obliterans.

Background: Thromboangiitis obliterans (TAO) or Buerger disease is a recurring progressive segmental vasculopathy that presents with inflammation and thrombosis of small and medium arteries and veins of the hands and feet. The exact cause remains unknown, with tobacco use (primarily smoking but also smokeless tobacco) being highly associated with the disease. The diagnosis is clinical and the lack of a diagnostic gold standard is a deterrent to diagnosing it in patients with atypical presentations. Obliterative endarteritis occurs perhaps due to a mixture of thrombosis and inflammation. The diagnostic sensitivity and specificity of D-dimer as a biomarker for thrombosis is well reported from its use in other areas such as deep vein thrombosis. Identification of a biomarker linked to the causation yields a diagnostic adjunct with a role in therapeutic decision-making, aiding diagnosis in atypical presentation, monitoring disease activity and gauging response to therapy. Methods: Between April 2014 and May 2015, we studied serum D-dimer (a marker of thrombosis) in 62 patients with TAO and compared this to 330 normal age- and sex-matched controls. We included all patients with peripheral arterial disease clinically diagnosed to have TAO according to the Shionoya criteria. There was no history of thrombosis or arterial disease in the control group. The control group was matched for baseline characteristics such as age and sex. All patients underwent a standard diagnostic protocol including blood tests (haemoglobin and creatinine), electrocardiogram, chest X-ray and ankle brachial pressure index. Blood was collected using an evacuated tube system into a citrate anticoagulant tube for testing D-dimer. Results: All the 62 patients diagnosed to have TAO were men with an average age of 40 years (range 18-65 years). They all had a history of tobacco use and did not have other atherogenic risk factors (part of the diagnostic criteria). Medium-vessel involvement was present in 53 patients (85%) and the rest presented with additional involvement of the popliteal and femoral vessels. Upper limb involvement or superficial thrombophlebitis was present in 95% of patients. Laboratory and imaging studies were consistent with TAO. The groups were well matched for age (p = 0.3). The median and interquartile range for D-dimer values were 61 ng/ml and 41-88 ng/ml in controls (n = 330) and 247 ng/ml and 126478 ng/ml in patients (n = 62), respectively (p<0.001). Conclusions: D-dimer levels are considerably elevated in patients with TAO. This indicates an underlying thrombotic process and suggests its potential role as a diagnostic adjunct. It also leads us to hypothesize a potential therapeutic benefit of anticoagulants in this disease.

Thromboangiitis obliterans episode: autoimmune flare-up or reinfection?

BACKGROUND: The possible role of infectious pathogens in the development of thromboangiitis obliterans (TAO) was considered soon after the disease was first described. However, it is not yet known whether infectious pathogens induce thrombotic vasculitis or if they cause a type of autoimmune disease. To investigate whether TAO relapses are more likely due to reinfection or autoimmune flare, the serum levels of toll-like receptor (sTLR) 4, sTLR2, C-reactive protein (CRP), and neopterin were evaluated in TAO patients during both the acute and quiescent phases of the disease as well as in a gender-, age-, and smoking habit-matched control group. METHODS: Following a cross-sectional study design, 28 patients in the acute phase of TAO and 23 patients in the quiescent phase participated in this study. In addition, 31 matched controls were enrolled. RESULTS: Toll-like receptor (TLR) 4 was significantly higher in patients in the acute phase of the disease than in patients in the quiescent phase (P=0.012). Also, TLR4 was significantly higher in the patients with CRP >7 µm/mL than in the patients with lower CRP (P=0.031). Notably, TLR4 in the patients in the quiescent phase of TAO was significantly lower than in the controls (P=0.006). No significant difference in the level of TLR2 was found among the groups (P>0.05). Neopterin was significantly higher in the acute phase of TAO in comparison to the quiescent phase (P=0.003) and the controls (P=0.005). CONCLUSION: These findings indicate that the trigger of TAO might be Gram-negative bacteria, which can be hidden or immunologically suppressed in the quiescent phase of TAO, leading to a lower level of TLR4 accompanying the normal level of neopterin. However, relapses might develop according to toxic or hypoxic cell injuries. Hence, TLR4 shedding will increase, and therefore, sTLR4 could become closer to the level demonstrated in the controls.

Investigation of Asymmetric and Symmetric Dimethylarginine Levels after Iloprost Treatment in Patients with Buerger's Disease.

OBJECTIVE: The aim of this study was to compare the levels of acetyl-dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and the l-arginine/ADMA ratio before and after iloprost treatment in patients with Buerger's disease. METHODS: Between January 2011 and December 2015, data from 44 patients (36 males, 8 females, mean age 48.7 ± 18.1 years) with the diagnosis of Fontaine Stage III-IV Buerger's disease were included. Iloprost infusion was administered intravenously through the forearm veins for 7 days at a dose of 0.5-1.5 ng/kg/min over 16 h. Blood samples were collected before and after treatment for measurement of ADMA, SDMA, and l-arginine. ADMA, SDMA, l-arginine levels were measured using high performance liquid chromatography (HPLC). RESULTS: After iloprost treatment, ADMA and SDMA levels significantly decreased (p = .001). The increase in the l-arginine levels was not significant (p = .16). However, the l-arginine/ADMA ratio increased significantly (p = .001). CONCLUSION: Iloprost treatment decreases ADMA and SDMA, which are associated with endothelial dysfunctions in patients with Buerger's disease. Of note, the still higher than normal range of SDMA levels after iloprost treatment suggests that treatment should continue until SDMA levels are within the normal range in this patient population.

Rickettsia infection could be the missing piece of the Buerger's disease puzzle.

BACKGROUND: Rickettsia was suggested as a possible etiology of Buerger's disease (BD) in the 1980s but this suggestion was never ruled out or proven. Recently, we found evidence of Rickettsia by polymerase chain reaction in 3 out of 25 biopsy samples from the amputated limb of a young man diagnosed with BD. The aim of this paper was to investigate the presence of anti-rickettsial antibodies in the sera of BD patients. METHODS: To detect the IgG class antibody against Rickettsia rickettsii, which has cross reactions with the spotted fever group (RSFG), and Rickettsia typhi, which has cross reactions with typhus fever group, the sera of patients and controls were diluted to 1:64 and analyzed by indirect micro fluorescence immunoassay (MIF). RESULTS: The MIF study showed that 26 of the 28 patients were positive for Rickettsia rickettsii antibodies and MIF had the same appearance as the positive control, which was provided with the kit. In all members of the healthy control group, Rickettsia rickettsii was negative and had the appearance of the negative control. Rickettsia typhi was negative for all patients and members of the control group. CONCLUSIONS: A species of Rickettsia associated with the RSFG, which might not be pathogenic for the entire population, may induce BD in the context of a specific genetic or environmental background. RSFG infection could explain key questions about BD, including its gender and geographical distribution, clinical manifestation, angiography pattern, and pathological findings. Evaluating antibodies against RSFG in BD patients from different countries is now highly recommended.

Coexistence of axial spondyloarthritis and thromboangiitis obliterans in a young woman.

A peculiar coexistence of axial spondyloarthritis and ischemia of the feet and the fourth finger of the left hand in a young woman, who was a heavy smoker, is discussed in this report. This picture was considered within the context of thromboangiitis obliterans. Positivity of anti-nuclear antibodies and mild elevation of inflammatory parameters were noted. Computed tomography angiograms of upper and lower limbs showed luminal narrowing and occlusion of the left humeral, left anterior/posterior tibial and right anterior tibial arteries. Daily iloprost perfusions were started, and smoking cessation was strongly recommended. Coldness and rest pain in the distal extremities improved within a few weeks. The possibility that spondyloarthritis might precede the clinical picture of thromboangiitis obliterans should be considered in heavy smokers.

Noninvasive Transcutaneous Monitoring in Long-Term Follow-Up of Patients With Thromboangiitis Obliterans Treated With Intravenous Iloprost.

We evaluated the effectiveness of intravenous iloprost (IVI) in outpatients with thromboangiitis obliterans (TAO) and lower limb noninvasive transcutaneous monitoring (TCM) at follow-up (FU). Ten consecutive patients with TAO underwent IVI therapy. Transcutaneous oxygen (TcPo 2) and carbon dioxide (TcPco 2) determination and laser Doppler flowmetry (LDF) were performed before and after IVI at 3, 6, and 12 months of FU. Clinical response was positive in 7 patients, whereas 3 nonresponders underwent a second IVI cycle with 1 showing a late positive clinical response. After 12 months of FU, all patients were alive without amputations. Supine and dependent TcP2 levels significantly improved (P < .005). Hallux LDF values showed significant change with the maximal hyperemic test at 44°C (P < .005). Forefoot maximal hyperemic test at 44°C LDF (P < .005) and improved venous arterial reflex (P < .05) showed statistically significant time evolution. We demonstrated some degree of IVI effectiveness and evaluated TCM in patients with TAO.

Sera of patients with thromboangiitis obliterans activated cultured human umbilical vein endothelial cells (HUVECs) and changed their adhesive properties.

INTRODUCTION: The aim of this study was to investigate the impact of thromboangiitis obliterans (TAO) sera on activation of primary cultures of human umbilical vein endothelial cells (HUVECs) as a model for vascular endothelial cells. METHODS: Study subjects included 21 TAO patients as the case group and 20 healthy smokers and 17 healthy non-smokers as control groups. Case and control groups were matched based on their age, socioeconomic status and smoking habit. HUVECs were incubated with the sera of case and control groups and gene expression of intercellular adhesion molecule (ICAM-1) and vascular adhesion molecule (VCAM-1) were evaluated by real-time polymerase chain reaction, TaqMan method. RESULTS: The expression of ICAM-1 and VCAM-1 were significantly higher in HUVECs after incubation with TAO sera compared to control groups (P < 0.05). VCAM-1 had a significant correlation with duration of smoking (P < 0.001, R = 0.672), while the expression of ICAM-1 had a significant correlation with the number of cigarettes smoked daily (P = 0.04, R = 0.421). CONCLUSION: Sera from TAO patients could activate HUVECs. This same activation might occur in vivo by the responsible cytokines, in particular those released from activated platelets, free oxygen radicals, and possibly low levels of nitric oxide (NO) of the sera of TAO patients, as a consequences of chronic cigarette smoking and of endothelial NO synthase polymorphism. Therefore, plasma exchange might be helpful in acute phase of the disease for saving the limbs and administration the combinations of exogenous NO with anti-oxidants might be helpful in long-term management of TAO patients to reduce the risk and rate of amputation.

Oxidative and antioxidative pathways might contribute to thromboangiitis obliterans pathophysiology.

Higher oxidative and lower antioxidative markers have been reported in patients with thromboangiitis obliterans (TAO) when compared with healthy control groups. However, the recent literature has not compared the results with healthy smokers, despite the observed effects of cigarette smoke on oxidative and antioxidative pathways. The aim of this study was to determine the oxidative stress status in TAO patients compared with healthy smokers, through direct assessment of the pro-oxidant-antioxidant balance (PAB) assay. The study included 21 patients with TAO, 19 smokers and 17 non-smokers. Comparison between groups revealed a significant increase in PAB value in the TAO group when compared with the smoker (P= 0.001) and non-smoker (P< 0.001) groups. About 95% of TAO cases had PAB value more than 50 units. The PAB value more than 50 might increase the relative risk of TAO presentation about seven folds (relative risk [RR]= 7.464, confidence interval [Cl]= 95%). The increased PAB value in the TAO might be due to impairment of the oxidative and antioxidative pathways. Based on this hypothesis, the effect of cigarette smoke on oxidative stress might be exaggerated in TAO and may lead to inflammatory and thrombotic events. Further studies for evaluating antioxidant therapies on the outcome of TAO are recommended.

Investigation of the expression of mediators of neovascularization from mononuclear leukocytes in thromboangiitis obliterans.

The aim of this study was to investigate the expression of the cytokines, chemokines and effective molecules of peripheral blood mononuclear cells (PBMCs) that play a role in neovascularization in thromboangiitis obliterans (TAO). Lymphocytes from TAO patients (n = 20) and control subjects (healthy smokers [n = 16] and non-smokers [n = 17]) were evaluated using realtime polymerase chain reaction in order to examine the mRNA expression of CXCL1 and interleukin 8 (IL-8; inducers of collateral development by recruitment of circulating progenitor cells [CPCs]), endothelial cell growth factor A (VEGF-A) and inducible nitric oxide synthase (iNOS; inducers of angiogenesis) and interferon gamma (IFN-γ) and vascular endothelial growth factor receptor 1 (VEGFR-1; inhibitors of angiogenesis). CXCL1 expression was significantly higher in the TAO patients than control subjects. The expressions of IL-8, VEGFR-1 and IFN-γ were significantly higher in the TAO patients and smokers than in non-smokers. However, no differences in iNOS and VEGF-A expression were noted. In conclusion, PBMCs from TAO patients expressed cytokines that potentially recruit CPCs and promote arteriogenesis. However, TAO patients typically have low CPC levels, perhaps due to high oxidative stress. Further studies are recommended in order to investigate the efficacy of antioxidant therapy on the outcome of TAO before administration of angiogenic factors.

Plasma levels of homocysteine in Buerger's sufferers and healthy heavy smokers and non-smokers.

BACKGROUND: Our aim of this study was to evaluate the possible association between homocysteine levels and Buerger's disease in a case-control study. METHODS: 25 patients with Buerger's disease based on Shionoya's clinical criteria, and 25 heavy smokers along with 25 healthy non-smokers (control) were recruited for this study. All groups were matched for age. Plasma homocysteine levels were measured in each patient and then compared between the three groups. RESULTS: The mean plasma concentration of homocysteine was 16.88 mmol/L in the Buerger sufferers; as for the smoker (group 2) and control (group 3) groups, the level was as low as 13.89 and 13.56 mmol/L, respectively. CONCLUSIONS: Patients with thromboangiitis obliterans, especially those with a progressive course, benefit from the hyperhomocysteinemia screening test.

Assessment of plasma prothrombotic factors in patients with Buerger's disease.

The pathogenesis of Buerger' disease (thrombangiitis obliterans; TAO) remains unknown, although a strong association with tobacco use has been established. Blood coagulation and fibrinolytic factors as well as selected clinical chemistry parameters have been evaluated in 37 patients with Buerger's disease. Median levels of prothrombotic factors were higher in patients with TAO than in healthy control: annexin V (P < 0.0003), factor VII (P < 0.0001), factor VIII (P < 0.0000001), factor XI (P < 0.000003), homocysteine (P < 0.014) and fibrinogen (P = 0.00007). Patients with Buerger's disease also showed higher median plasma levels of urokinase type plasminogen activator (uPA) (P < 0.000004), its receptor (uPAR) (P < 0.0008) and uPA complex with plasminogen activator inhibitor 1 (uPA-PAI-1) P < 0.000006). In contrast, plasma concentrations of apolipoprotein A and folic acid were lower in patients with TAO than in control (P < 0.004 and P < 0.0006; respectively). Higher plasminogen (P < 0.05) and cholesterol (P < 0.003), as well as lower folic acid (P < .0.05) levels were noted in the smokers group than in nonsmoking patients. We found higher plasminogen (P < 0.05), factor VII (P < 0.05), total lipids (P < 0.003), cholesterol (P < 0.05) and triglycerides (P < 0.002) levels in patients requiring surgical treatment for limb-threatening ischaemia than the patients treated only conservatively. These findings suggest an important role of haemostatic risk factors in the pathogenesis of Buerger's disease, with special regard to hyperhomocysteinemia that might be aggravated by low serum folic acid level. In patients with aggressive clinical course, disturbances in serum lipids were more pronounced. Further studies are warranted to establish whether diet supplementation of folic acid as well as normalization of lipids balance might influence the clinical course of TAO.

Activation of cytokines corroborate with development of inflammation and autoimmunity in thromboangiitis obliterans patients.

Thromboangiitis obliterans (TAO) is a segmental inflammatory occlusive disorder that affects the arm and leg arteries of young smokers. The immune system seems to play a critical role in the aetiology of TAO; however, knowledge of the aspects involved in the progression of vascular tissue inflammation and, consequently, the evolution of this disease is still limited. This study was carried out to investigate the cytokine levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-4, IL-17 and IL-23 in the plasma of TAO patients presenting with acute clinical manifestations. The study included 20 TAO patients (n = 10 women; n = 10 men) aged 38-59 years under clinical follow-up, classified into two groups: (i) TAO former smokers (n = 11) and (ii) TAO active smokers (n = 9); the control groups included normal volunteer non-smokers (n = 10, active smokers (n = 10) and former smokers (n = 10). Patients' plasma samples were measured using the sandwich enzyme-linked immunosorbent assay. Statistical analyses were performed using the non-parametric Mann-Whitney U-test, with parameters significant at P < 0·05. The activities of all cytokines were different in groups of TAO patients when compared with normal controls, and decreased for control smokers. Increased levels of TNF-α, IL-1ß, IL-4, IL-17 and IL-23 were significant in patients with TAO when compared to the controls (P < 0·005, all parameters). The results presented here indicate an increased production of cytokines in TAO, possibly contributing to the inflammatory response observed in the patients' vascular levels. In addition, the increased levels of IL-17 and IL-23 suggest that the disturbance of TAO is involved with mechanisms of autoimmunity. Thus, the discovery of IL-17 and its association with inflammation and autoimmune pathology has reshaped our viewpoint regarding the pathogenesis of TAO, which was based previously on the T helper type 1 (Th1)-Th2 paradigm.

Circulating angiogenic factors in patients with thromboangiitis obliterans.

BACKGROUND: Thromboangiitis obliterans (TAO, also known as Buerger's disease) is a non-atherosclerotic inflammatory vascular disease that primarily affects arteries in the extremities of young adult smokers. Since the etiology of TAO is still unknown, therapeutic options are limited. Recent attempts in therapeutic angiogenesis have been promising. Therefore, the aim of our study was to evaluate angiogenic processes and factors including circulating progenitor cells in TAO. METHODOLOGY/PRINCIPAL FINDINGS: TAO patients with critical limb ischemia and age- and gender-matched nonsmokers and smokers without cardiovascular disease (n = 12 in each group) were enrolled in the study. Flow cytometric analysis of peripheral blood showed significantly decreased levels of circulating CD45(dim)CD34(+) progenitor cells in TAO patients and in smokers compared to nonsmokers. In contrast to both control groups, the proportion of CD45(dim)CD34(+) progenitor cells co-expressing VEGF receptor-2 (VEGFR2) was significantly elevated in TAO patients. Enzyme-linked immunosorbent assay (ELISA) of common angiogenic factors (such as VEGF) did not clearly point to pro- or antiangiogenic conditions in serum or plasma of TAO patients. Serum of TAO patients and controls was evaluated in proliferation, migration (scratch assay) and spheroid sprouting assays using human umbilical vein endothelial cells (HUVECs). Serum of TAO patients exhibited a diminished sprouting capacity of HUVECs compared to both control groups. Proliferation and migration of endothelial cells were impaired after treatment with serum of TAO patients. CONCLUSION: Levels of circulating progenitor cells were altered in TAO patients compared to healthy nonsmokers and smokers. Furthermore, serum of TAO patients exhibited an antiangiogenic activity (impaired endothelial cell sprouting, migration and proliferation) on endothelial cells, which may contribute to vascular pathology in this patient population.

Imbalanced matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 activities in patients with thromboangiitis obliterans.

The pathogenic mechanisms of thromboangiitis obliterans (TAO) are not entirely known and the imbalance of matrix metalloproteinases (MMPs) plays a role in vascular diseases. We evaluated the MMP-2 and MMP-9 circulating levels and their endogenous tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in TAO patients with clinical manifestations. The study included 20 TAO patients (n = 10 female, n = 10 male) aged 38-59 years under clinical follow-up. The patients were classified into two groups: (1) TAO former smokers (n = 11) and (2) TAO active smokers (n = 9); the control group included normal volunteer non-smokers (n = 10) and active smokers without peripheral artery disease (n = 10). Patient plasma samples were used to analyze MMP-2 and MMP-9 levels using zymography, and TIMP-1 and TIMP-2 concentrations were determined by enzyme-linked immunosorbent assays. The analysis of MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios (which were used as indices of net MMP-2 and MMP-9 activity, respectively) showed significantly higher MMP-9/TIMP-1 ratios in TAO patients (p < 0.05). We found no significant differences in MMP-2/TIMP-2 ratios (p > 0.05). We found higher MMP-9 levels and decreased levels of TIMP-1 in the TAO groups (active smokers and former smokers), especially in active smokers compared with the other groups (all p < 0.05). MMP-2 and TIMP-2 were not significantly different in patients with TAO as compared to the control group (p > 0.05). In conclusion, our results showed increased MMP-9 and reduced TIMP-1 activity in TAO patients, especially in active smokers compared with non-TAO patients. These data suggest that smoke compounds could activate MMP-9 production or inhibit TIMP-1 activity.

Asymmetric dimethylarginine levels in Buerger's disease.

BACKGROUND: Endothelial dysfunction may play a major role in both peripheral arterial disease (PAD) and Buerger's disease (BD). Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase and increased ADMA levels impair vascular homeostasis. We aimed to determine the plasma levels of ADMA and evaluate the relationship of ADMA levels with smoking and clinical severity of the disease in patients with BD and to compare these results with those of patients with PAD and healthy individuals. METHODS: In our center, 45 patients undergoing peripheral arterial surgery, 28 patients being followed up for BD, and 24 healthy individuals without vascular or cardiac disease, were enrolled in the study. Intra- and intergroup analysis was performed to evaluate the relationship of ADMA levels with smoking behaviors and clinical disease severity according to Fontaine classification. RESULTS: ADMA levels were 1.26 ± 0.76 mmol/L, 0.87 ± 0.27 mmol/L, and 1.07 ± 0.88 mmol/L in patients with PAD, in patients with BD, and in the control group, respectively. ADMA levels were significantly higher in patients with PAD than those in control patients (p = 0.003) and the levels observed in patients with BD were significantly lower than those in control patients (p = 0.001). Smokers with PAD had higher ADMA levels than smokers with BD (p = 0.03). ADMA levels were higher in patients with Fontaine stage III and IV disease than those with Fontaine stage II diseases, for patients with PAD as well as those with BD. CONCLUSION: The lower ADMA levels observed in patients with BD might be related to the degradation of ADMA by dimethylarginine dimethylaminohydrolase in response to ischemia and could act as a defensive mechanism during the acute or quiescent phases. In patients with BD experiencing severe clinical conditions or with a longer time course for the disease, higher ADMA levels may suggest a poor prognosis.

Trace elements and toxic heavy metals play a role in Buerger disease and atherosclerotic peripheral arterial occlusive disease.

AIM: The aim of the present study was to define the roles of trace elements and toxic heavy metals in Buerger disease and atherosclerotic peripheral arterial occlusive disease (PAOD). METHODS: Seventy-five subjects who were identical in demographic charecteristics were selected for the study; 25 with Buerger disease, 25 with PAOD, 25 healthy volunteers. Serum selenium (Se), zinc (Zn), copper (Cu), iron (Fe),whole blood cadmium (Cd) and lead (Pb), erythrocyte glutathione (GSH), erythrocyte glutathione peroxidase (GSH-Px), erythrocyte and plasma malondialdehyde (MDA) levels were measured. RESULTS: Serum Se and Zn levels were significantly low in patients with Buerger disease compared to patients with PAOD and controls (P<0.001 and P<0.001 respectively). Serum levels of Fe and Zn were also significantly low in patients with PAOD compared to controls (p<0.001 and p<0.05 respectively). In contrast, Cu and Pb levels in Buerger disease group were significantly high compared to PAOD and control groups (P<0.001 and P<0.001 respectively). Erythrocyte GSH and GSH-Px levels were significantly lower in patients with Buerger disease compared to patients with PAOD and controls (P<0.001 and P<0.001 respectively), while erythrocyte and plasma MDA levels were significantly higher (P<0.001 and P<0.001 respectively). CONCLUSION: It can be concluded that the levels of trace elments and toxic heavy metals and oxidative stress influence the disease process in Buerger disease more than PAOD.