Relation of kynurenine/tryptophan with immune and inflammatory markers in coronary artery disease.

BACKGROUND: Inflammation and immune activation have a crucial role in the pathogenesis of cardiovascular diseases. Indolamine 2,3-dioxygenase, a tryptophan catabolising enzyme, is up-regulated with various inflammatory stimuli. The aim of this study was to evaluate the relationship of tryptophan degradation with immune and inflammatory markers in coronary artery disease. METHODS: 57 subjects undergoing coronary angiography were recruited. 18 subjects with normal coronary arteries according to Gensini scoring were selected as a control group and the rest of subjects were included in patient group. Serum tryptophan and kynurenine levels were determined with HPLC-UV method, and kynurenine/tryptophan ratio was evaluated as IDO activity. Serum neopterin and myeloperoxidase activity were measured by ELISA method. RESULTS: While the kynurenine/tryptophan ratio and neopterin levels were similar in both groups, the patient group had higher myeloperoxidase and hs-CRP levels than controls (p = 0.02, p = 0.002, respectively). The kynurenine/tryptophan ratio was correlated with neopterin in both groups (r = 0.389, p = 0.025; r = 0.683, p = 0.002, respectively) and with hs-CRP in patients (r = 0.637, p = 0.001). Also, neopterin levels were correlated with hs-CRP in patients (r = 0.755, p = 0.0001). CONCLUSIONS: Our results are in line with a role of inflammation in coronary artery disease. The study provides evidence that IDO activity is related with immune and inflammatory states. Also, the study was performed in a limited hospital-based population. Further studies are warranted in the larger groups.

Influence of gender on C-reactive protein, fibrinogen, and erythrocyte sedimentation rate in obstructive sleep apnea.

Inflammation is one of the pathophysiological pathways suggested for the development of cardiovascular disease in obstructive sleep apnea (OSA). The recurrent nocturnal episodes of hypoxia/reoxygenation observed in patients with OSA appear to be partly responsible for the systemic inflammatory response. The aim of this study was to investigate the role of inflammation by measuring the C-reactive protein (CRP) and fibrinogen levels, and erythrocyte sedimentation rate (ESR) in the OSA according to gender. This study included 139 apparently healthy subjects with newly diagnosed OSA and 27 control subjects who underwent overnight polysomnography and routine blood tests. Levels of inflammatory markers (CRP, fibrinogen, and ESR) were determined from the blood samples taken in the morning. The levels of CRP and fibrinogen were significantly higher in patients than in controls (p<0.0001 and p=0.001, respectively). Fibrinogen and ESR were significantly higher in the female patients than in the male patients (p<0.0001). In female patients, CRP and ESR correlated with time spent at oxygen saturation (T%SaO2)<90 (R=0.327, p=0.029 and R=0.301, p=0.05, respectively), T%SaO2<85 (R=0.482, p=0.001 and R=0.409, p=0.006, respectively), oxygen desaturation index (ODI) (R=0.298, p=0.047 and R=0.340, p=0.026, respectively), lowest oxygen saturation (SaO2) (R=-0.293, p=0.051 and R=-0.374, p=0.013, respectively), mean SaO2 (R=-0.408, p=0.005 and R=-0.385, p=0.011, respectively). In male patients, CRP correlated with T%SaO2<90 (R=0.267, p=0.009), T%SaO2<85 (R=0.279, p=0.006), mean SaO2 (R=-0.284, p=0.006) and fibrinogen correlated with T%SaO2<90 (R=0.282, p=0.028), and mean SaO2 (R=-0.252, p=0.05). In conclusion, increased values of systemic inflammatory markers and their correlations with sleep data observed in our study support other studies suggesting the possible involvement of inflammation in OSA. As this correlation is more apparent in female patients then the males, it suggests that there may be a stronger relation between OSA development and inflammation in females. Higher levels of CRP, fibrinogen, and ESR may result from the combined interactions of obesity, metabolic syndrome (MetS) and nocturnal hypoxia.

Serum homocysteine levels and sildenafil 50 mg response in young-adult male patients without vascular risk factors.

The aim of the present study was to investigate serum homocysteine levels in patients with erectile dysfunction and to evaluate the relationship between serum homocysteine levels and response to the standard 50 mg phosphodiesterase 5 inhibitor treatment. Twenty-eight erectile dysfunction patients having normal vascular parameter according to Penile Doppler Ultrasonography and twenty healthy subjects were enrolled in the study. All subjects filled The International Index of Erectile Function (IIEF) questionnaire. A total of 4-6 doses of phosphodiesterase 5 inhibitor (sildenafil 50 mg) were given to patients. Later, they were divided into two groups as sildenafil responder and non-responder. Serum homocysteine levels were compared in groups based on sildenafil response. Compared with healthy subject, higher homocysteine levels were observed in patients with erectile dysfunction (p = 0.005), especially in sildenafil non-responder group (p = 0.005). There was significant negative correlation between homocysteine and IIEF scores in group responder to sildenafil treatment (r = -0.698, p = 0.008). Mean IIEF scores of patients with non-responder to sildenafil 50 mg were lower than those of controls (p = 0.0001), but mean IIEF scores of patients with responders approached values observed in control subjects (p = 0.002). The results indicated that measurement of serum homocysteine levels could be used as a marker for the evaluation of efficacy of phosphodiesterase 5 inhibitor and the selection of efficacious alternative therapies.

Accumulation of an endogenous inhibitor of nitric oxide synthesis and oxidative DNA damage in end-stage renal disease.

BACKGROUND: Elevated oxidative status and reduced antioxidant defence systems in patients with chronic renal failure (CRF) accelerate the prevalence of atherosclerosis and other chronic complications. We aimed to investigate the levels of reactive oxygen, nitrogen species, and antioxidants in patients with end-stage renal disease (ESRD) having hemodialysis and controls and evaluate the factors that might influence the oxidative-antioxidative balance. METHODS: Sixty four patients with ESRD were enrolled in this study. Twenty two controls with normal renal function were included. 8-hydroxy-2'-deoxyguanosine, asymmetric dimethylarginine, and nitrotyrosine levels were quantitated by Elisa. Catalase was assayed with a colorimetric method. Glutathione, nitric oxide, total antioxidant capacity, and lipid hydroperoxide were assayed spectrophotometrically. RESULTS: 8-hydroxy-2'-deoxyguanosine, asymmetric dimethylarginine, nitrotyrosine, and nitric oxide levels of patients were higher than those of the control group (p < 0.01) (p < 0.001), respectively. Total antioxidant capacity and catalase activity were significantly increased in controls compared to patients with renal failure (p < 0.001) (p < 0.01), respectively. CONCLUSIONS: Our data confirmed the previous findings that an increase in oxidative stress may be considered as one of the major risk factors in CRF patients. The lowering of total antioxidant defences in patients with end-stage renal disease on hemodialysis may contribute to the increased oxidative damage and to the development of renal complications.

Increased oxidative DNA damage and impaired antioxidant defense system in patients with gastrointestinal cancer.

BACKGROUND: Highly active intermediates are formed in aerobic metabolism which in turn leads to cellular damage. It is increasingly proposed that free radicals play a key role in human cancer development. The aim of this study was to investigate changes in 8-hydroxy-deoxyguanosine, nitrite+nitrate, total glutathione, total antioxidant capacity levels and superoxide dismutase, catalase, glutathione peroxidase activities in operative patients with gastrointestinal cancer before and after surgery and compare with inoperative patients. METHODS: Oxidative stress parameters were measured in 59 gastrointestinal cancer patients and 20 controls. 8-hydroxy-deoxyguanosine was quantitated by Elisa method. Superoxide dismutase, catalase, glutathione peroxidase were assayed with colorimetric methods; Nitrite+nitrate, total glutathione and total antioxidant capacity were assayed with spectrophotometric methods. RESULTS: 8-hydroxy-deoxyguanosine levels in cancer patients were higher than those of control group (p<0.01). Similarly, glutathione levels were increased compared with controls (p<0.01). However, nitrite+nitrate, total antioxidant capacity levels and superoxide dismutase and catalase activities were decreased in cancer patients compared with controls (p<0.01, p<0.01, p<0.05, p<0.01, respectively). The patients were divided into two groups; operative (n = 30) and inoperative (n = 29). A significant difference was found in inoperative group compared with postoperative group according to glutathione peroxidase activity (p<0.05). DISCUSSION: Our results demonstrate that the oxidant/antioxidant balance was altered in favor of free radicals and DNA damage in gastrointestinal cancer patients. Significant increases in 8-hydroxy-deoxyguanosine, glutathione and decreases in nitrite+nitrate, SOD, CAT activities and antioxidant molecules suggest the possible involvement of oxidative stress in gastrointestinal cancer. Glutathione peroxidase activities in postoperative patients were higher compared to inoperative patients.

Tryptophan degradation and neopterin levels in treated rheumatoid arthritis patients.

Increased kynurenine/tryptophan-reflects trytophan degradation-and neopterin levels have been regarded as a biochemical marker of cell-mediated immune response and inflammation. This study was designed to evaluate the usefulness of tryptophan degradation and neopterin levels in active rheumatoid arthritis patients under therapy. In this case-control study, kynurenine and tryptophan levels were determined by HPLC; neopterin and tumor necrosis factor-α levels were measured with ELISA in 32 active rheumatoid arthritis patients and 20 healthy controls. Although mean values of tryptophan, kynurenine, ratio of kynurenine to tryptophan, neopterin, and tumor necrosis factor-α levels did not show statistically significant differences between patient and control groups, neopterin levels correlated positively with kynurenine (r = 0.582, p < 0.02), kynurenine/tryptophan (r = 0.486, p < 0.05), erythrocyte sedimentation rate (r = 0.472, p < 0.05) and RF (r = 0.478, p < 0.05) in the rheumatoid arthritis group. CRP levels of the patient group correlated with kynurenine levels (r = 0.524, p < 0.03). Determination of tryptophan degradation and neopterin levels in chronic inflammatory disease may provide a better understanding of progression of the disease.

Variability of total thiol compounds, oxidative and nitrosative stress in uncomplicated pregnant women and nonpregnant women.

PURPOSE: The objective of this study was to determine the changes in total plasma thiols (homocysteine, cysteine and cysteinylglycine), lipid peroxidation and nitric oxide concentrations during normal pregnancy. METHODS: These variables were measured in 28 uncomplicated pregnant women at first, second and third trimesters and in 19 nonpregnant women. RESULTS: The mean concentrations of homocysteine, cysteine and cysteinylglycine were significantly lower in all trimesters of pregnancy compared with nonpregnant controls. There was significant elevation in serum lipid peroxidation levels of pregnant women within first and third trimesters compared with nonpregnant women. In spite of increase in mean nitric oxide levels in pregnant women, this increase did not reach statistically significant levels. CONCLUSION: This study provides information about the changes in plasma levels of many variables having important role in pregnancy complication during all trimesters in uncomplicated pregnancy compared with nonpregnant women.

Increased levels of 8-hydroxydeoxyguanosine and its relationship with lipid peroxidation and antioxidant vitamins in lung cancer.

BACKGROUND: Reactive oxygen species produced either endogenously or exogenously can attack lipids, proteins and DNA in human cells and cause potentially deleterious consequences. In recent years, their role in the pathogenesis of lung cancer and the preventive effect of antioxidants have been studied extensively. In this study, our aim was to investigate the levels of 8-hydroxy-2'-deoxyguanosine (8OHdG) and malondialdehyde as a marker for the effects of reactive oxygen species on DNA and lipids, the levels of antioxidant vitamins and the correlations between these oxidative stress markers and antioxidants in lung cancer. METHODS: Serum malondialdehyde, beta-carotene, retinol, and vitamins C and E were measured by high-performance liquid chromatography methods in fasting blood samples and 8OHdG was measured by gas chromatography-mass spectrometry in 24-h urine samples of patients with lung cancer (n=39) and healthy controls (n=31). RESULTS: The levels of 8OHdG and malondialdehyde were significantly higher (p<0.05 and p<0.005, respectively) and beta-carotene, retinol, and vitamins C and E (p<0.0001, p<0.0001, p<0.0001, and p<0.05, respectively) were significantly lower in patients than in controls. There was a significantly positive correlation between 8OHdG and malondialdehyde (r=0.463, p=0.01) and a negative correlation between the levels of 8OHdG and retinol (r=-0.419, p=0.021) in the patient group. CONCLUSIONS: Our results demonstrate that the oxidant/antioxidant balance was spoiled in favor of lipid peroxidation and DNA damage in lung cancer patients. Significant increases in the levels of malondialdehyde and 8OHdG and decreases in the levels of antioxidants suggest the possible involvement of oxidative stress in lung cancer.

Circulating nitric oxide (NO), asymmetric dimethylarginine (ADMA), homocysteine, and oxidative status in obstructive sleep apnea-hypopnea syndrome (OSAHS).

Obstructive sleep apnea-hypopnea syndrome (OSAHS) with episodic hypoxia-reoxygenation is associated with increased cardiovascular morbidity and mortality. Therefore, increased homocysteine, asymmetric dimethylarginine (ADMA), oxidative status, and decreased nitric oxide levels have been implicated as possible mechanisms for development of cardiovascular diseases. We aimed to investigate changes in the levels of these substances in patients with OSAHS in comparison with nonapneic controls. Thirty-four OSAHS patients and 15 healthy controls were included in this study. In the blood samples, oxidative status and nitric oxide levels were measured with spectrophotometric methods. Plasma ADMA and homocysteine levels were determined by using high-performance liquid chromatography with fluorescence detection. Nitric oxide levels were significantly low in OSAHS patients (p < 0.05) and correlated with mean SaO(2) (r = 0.513, p < 0.002) and lowest SaO(2) (r = 0.363, p < 0.03). Oxidative status, ADMA, and homocysteine levels were higher in OSAHS patients, but difference did not reach statistical significance. After dividing patients into moderate (AHI = 5-29) and severe (AHI > or = 30) OSAHS groups, significantly increased homocysteine levels were observed in the severe OSAHS group (p < 0.05). Nitric oxide levels negatively correlated with oxidative status in total OSAHS patients (r = -0.415, p < 0.02) and also in severe OSAHS group (r = -0.641, p < 0.007). Hyperhomocysteinemia and diminished NO production may be causal factors in endothelial dysfunction seen in OSAHS and may explain the association between OSAHS and cardiovascular diseases. These modifiable factors should be monitored in patients suspected of having OSAHS.

Usefulness of homocysteine as a cancer marker: total thiol compounds and folate levels in untreated lung cancer patients.

BACKGROUND: Apart from being a risk factor for atherosclerotic cardiovascular diseases, the latest research suggests homocysteine as a marker for cancer. We aimed to explore the clinical utility of plasma homocysteine levels as a marker in lung cancer. PATIENTS AND METHODS: Changes in serum total thiols and folate levels were investigated in newly diagnosed untreated lung cancer patients (n = 37) and compared with healthy controls (n = 26). Fluorometric HPLC methods were used for the determination of thiols. Other parameters were determined with commercial diagnostic kits. RESULTS: Increased total homocysteine (t-Hcy), decreased total glutathione (t-GSH) and folate levels were observed in lung cancer patients compared with healthy controls. Total levels of thiols and folate did not show any significant difference between SCLC and NSCLC patients. However, there were significantly higher t-Hcy, lower t-GSH and folate levels in the advanced-stage group compared with controls. Prevalence of hyperhomocysteinemia was 65% in lung cancer patients when 12 micromol/l were taken as a cut-off value for t-Hcy levels. CONCLUSION: Homocysteine is suggested as a marker for several types of cancer, but our result did not support this hypothesis for lung cancer. Although higher homocysteine levels were observed in the present study, further investigation in the larger cancer population would clarify the importance of homocysteine as a cancer marker.

Assessment of homocysteine, neopterin and nitric oxide levels in Behçet's disease.

BACKGROUND: Behçet's disease is a multisystemic immunoinflammatory disease with a wide variety of clinical manifestations, whereas recurrent aphthous stomatitis is a local oral disease. The aim of this study was to examine the distribution of homocysteine levels in patients with active Behçet's disease, possible association of homocysteine with nitric oxide and neopterin levels, and to characterize the differences between patients with Behçet's disease and those with recurrent aphthous stomatitis in terms of these parameters compared with healthy controls. METHODS: A total of 23 patients with active Behçet's disease, 25 patients with recurrent aphthous stomatitis as positive controls, and 21 healthy subjects were included in this study. Serum homocysteine and neopterin levels were measured flourimetrically by HPLC. Serum nitric oxide production was assayed by measuring total nitrite levels with Griess reagent. RESULTS: Significantly higher homocysteine (12.9+/-3.3 micromol/L) and lower nitric oxide (41.5+/-10.9 micromol/L) and neopterin (6.4+/-1.0 nmol/L) levels were observed in patients with Behçet's disease compared with healthy controls (10.7+/-2.0 micromol/L, 49.7+/-16.2 micromol/L, 8.7+/-2.2 nmol/L, respectively) (p<0.03 for neopterin, p<0.04 for homocysteine and nitric oxide). However, homocysteine, nitric oxide, biopterin and neopterin levels and the neopterin/biopterin ratio for recurrent aphthous stomatitis patients were not significantly different compared to healthy controls. A significant positive correlation was observed between serum homocysteine and serum neopterin/biopterin ratio in patients with Behçet's disease (r=0.975, p<0.005). CONCLUSIONS: In contrast to recurrent aphthous stomatitis, there is a higher prevalence of hyperhomocysteinemia in Behcet's disease. Homocysteine may have deleterious effects on the pathology of Behcet's disease by decreasing nitric oxide levels and interfering with the immune system.

Oxidative status in rheumatoid arthritis.

The insufficiency of antioxidant defense systems and the acceleration of the oxidative reactions can be results of the pro-oxidant/antioxidant imbalance in rheumatoid arthritis (RA). The aim of our study was to investigate the changes in oxidant status by measuring two different parameters; one was the level of malondialdehyde (MDA) as an index of lipid peroxidation and the other was total oxidative status; we could then compare our results with the antioxidant status, superoxide dismutase (SOD) enyzme activities. All were assessed in 22 patients with active RA and 18 age- and gender-matched control subjects. While serum MDA levels were significantly increased in patients with RA compared to the control group (p<0.03), the total oxidative status levels were decreased in patients with RA compared to the control group (p<0.008), and serum SOD activities did not show any statistical difference between the two groups. In conclusion, the increased MDA levels in our study may be important as a marker but are not sufficient to conclude that there was an increase in oxidative stress in RA patients because supporting results were not obtained from SOD and oxidative status measurements. These results give further support to the concept of oxygen free radicals playing a role in the pathogenesis of chronic inflammatory disorders, but we also consider that there is a more complex relationship than has been assumed. We think that further studies are needed to clarify these conflicting results.

Increased plasma homocysteine and allantoin levels in coronary artery disease: possible link between homocysteine and uric acid oxidation.

OBJECTIVE: Homocysteine increases the damage to the cardiovascular system in different ways, one of them is the formation of reactive oxygen species resulting from the auto-oxidation of homocysteine. At the same time, uric acid is one of the major antioxidants in the plasma and protects the cells towards increased ROS activity. In humans, allantoin is only formed from non-enzymatic oxidation of uric acid by free radicals. We aimed to determine the levels of homocysteine, uric acid and allontoin in patients with coronary artery diseases, and to evaluate the possible correlation between homocysteine and allantoin. METHODS AND RESULTS: Plasma total homocysteine, uric acid and allantoin levels of 50 patients with coronary artery diseases and 23 healthy controls were determined by HPLC methods. Commercial diagnostic kits were used for the determination of other biochemical parameters. We obtained higher homocysteine, uric acid and allantoin levels in patients than in controls (p < 0.0001). Homocysteine levels were positively correlated with uric acid (r = 0.435, p < 0.0001) and allantoin (r = 0.583, p < 0.0001) levels in the whole study population. This correlation was persistent between allantoin and homocysteine after adjustment of these parameters for age, sex and creatinine. We accepted 15.0 micromol/l as a cut-off value between normal and mildly elevated homocysteine levels for patients and controls. Twenty-five patients showed moderate hyperhomocysteinaemia. The mean allantoin and uric acid values of the moderate hyperhomocysteinaemic group were significantly higher than that of the group having lower homocysteine levels than this cut-off value (p < 0.0001 for allantoin, p < 0.02 for uric acid). CONCLUSION: Results imply that there is increased allantoin production resulting from uric acid oxidation by free radicals in hyperhomocysteinaemic patients with coronary artery disease. The possible significance of the relationship between homocysteine and allantoin warrants further study.

Oxidative stress is decreased in off-pump versus on-pump coronary artery surgery.

Oxidative stress occurs in patients undergoing coronary artery bypass operation. The aim of this study was to investigate the difference in oxidative stress in off-pump versus on-pump coronary artery bypass surgery. In the present study, in serial blood samples, plasma malondialdehyde (MDA) as index of lipid peroxidation, red blood cells glutathione peroxidase (GPx) and superoxide dismutase (SOD) were measured to compare the extent of oxidative stress in 30 patients undergoing OPCAB (off-pump coronary artery bypass grafting), 12 patients undergoing CABG (on-pump coronary artery bypass grafting) and 18 healthy controls. In CABG group, MDA levels increased significantly from 2.87 +/- 0.62 nmol/mL before anesthesia and 2.87 +/- 0.65 nmol/mL after anesthesia to 3.05 +/- 0.66 nmol/mL after ischemia (p < 0.05). Similarly, SOD levels also elevated significantly from 661.58 +/- 78.70 U/g Hb before anesthesia and 659.42 +/- 81.21 U/g Hb anesthesia induction to 678.08 +/- 75.80 U/g Hb after ischemia (p < 0.01, p < 0.01, respectively). In OPCAB group, only SOD levels increased from 581.73 +/- 86.24 U/g Hb anesthesia induction to 590.90 +/- 88.90 U/g Hb after reperfusion (p < 0.05). Glutathione peroxidase levels were not changed according to blood collection times in both of CABG group or OPCAB group (p > 0.05). Our results show that only mild signs of oxidative stress is found after reperfusion in OPCAB operation compared with CABG operation. Further studies are needed in order to confirm this hypothesis.

The association between total antioxidant status and oxidative stress in Behçet's disease.

There has recently been growing evidence supporting the importance of oxidative stress in the pathogenesis of Behçet's disease (BD). In this study, we aim to evaluate total antioxidant status (TAS) and total oxidative stress (TOS) in BD patients, and compare their results both with controls that had recurrent aphthous stomatitis (RAS) and healthy controls. TAS statistically decreased in RAS patients, and TOS levels increased in BD and RAS patients than those in healthy controls. The serum levels of Cu significantly increased only in BD patients when compared with healthy controls. Fe levels were not statistically different among the BD patients, RAS patients and healthy controls, but there was a positive correlation between TOS and plasma Fe levels in BD patients. Our results suggest that there is an insufficient antioxidant system and increased oxidative status both in BD and RAS patients. The antioxidant supplementations in addition to medical treatments will improve the quality of life.

Lipid peroxidation and antioxidant status in blood and tissue of malignant breast tumor and benign breast disease.

Changes in the levels of malondialdehyde (MDA), nitrate and nitrite (as an index of nitric oxide production), lipid hydroperoxide (LOH), total antioxidant capacity (TAC), lipids (total cholesterol and triglycerides) and lipoproteins (HDL- and LDL-cholesterol) were estimated in breast cancer patients (n = 15) and benign breast disease (n = 15). Serum and tissue MDA levels were found to be decreased in breast cancer patients compared to the benign group (p < 0.05). In contrast, nitrate and nitrite levels were increased in serum and tissue of the cancer group compared to benign breast disease patients (p < 0.05). Compared to the benign group, tissue TAC levels were elevated in the breast cancer patient group (p < 0.05). Total cholesterol and HDL-cholesterol were elevated in the benign group compared with cancer patients (p < 0.05). These findings support the hypothesis that lipid peroxidation in serum and tissue of benign breast disease is greater than in breast cancer. However, the enhanced levels of nitric oxide may be in response to inflammation in patients with breast cancer. Total antioxidant status is lower in benign tissue than in cancerous tissue, probably to compensate for this elevated free radical production.

Urate oxidation during percutaneous transluminal coronary angioplasty and thrombolysis in patients with coronary artery disease.

Thrombolysis and percutaneous transluminal coronary angioplasty (PTCA) are kinds of procedures that can be used to restore the blood flow of previously ischemic myocardium that can be the result of excessive production of reactive oxygen and nitrogen species, such as superoxide and hydroxyl radical, hypochlorous acid and peroxynitrite. Reaction of urate with some of these potent oxidants results in allantoin production. In this study, we measured the serum allantoin levels, an oxidation product of urate, and "in vivo" marker of free radical generation in reperfusion of ischemic myocardium. After an overnight fasting state, blood samples were collected from 35 patients with coronary occlusive diseases (7 women and 28 men) and 31 healthy subjects (8 women and 23 men). Serum allantoin and urate levels were measured by a GC-MS method. Serum allantoin levels of patients on PTCA therapy (mean+/-SD, 27.4 +/- 15.2 micromol/l) and thrombolytic therapy (24.6 +/- 8.6 micromol/l) were significantly higher than those of the patients without therapy (15.8 +/- 6.2 micromol/l, p < 0.05 with PTCA and p < 0.006 with thrombolysis) and healthy controls (12.6 +/- 6.3 micromol/l, p < 0.002 with PTCA and p < 0.0001 with thrombolysis). Although serum urate levels in PTCA (380.1 +/- 72.6 micromol/l) and thrombolysis (359.5 +/- 60.0 micromol/l) were higher than those in the non-therapy patients (336.6 +/- 53.8 micromol/l) and controls (318.3 +/- 81.0 micromol/l), there were no significant differences among groups (p > 0.05). The results of the study are consistent with others which have demonstrated, higher urate levels are associated with coronary occlusive diseases. Our data support the hypothesis that generation of ROS occurs during myocardial reperfusion. Increased allantoin levels may be used as an index of increased oxidative stress during reperfusion.

Prevalence of zinc deficiency and immune response in short-term hemodialysis.

Zinc is an essential trace element for many biological functions, including immune functions. The mechanism by which zinc may affect the immune system is certainly multifaceted, due to zinc's widespread action on different enzymes, peptides, transcriptional factors and cytokines involved in the various physiological steps of immune development and reactivity. In this study, prevalence of zinc deficiency and alteration in complement system, immunoglobulins and T cell subsets depending on zinc levels were analyzed in short-term hemodialysis patients and compared with healthy controls. Plasma zinc levels were measured by flame atomic absorption spectrometry. Serum levels of complement C3 and C4, immunoglobulins G (IgG), M (IgM), and A (IgA), and prealbumin were measured by nephelometry depending on antigen-antibody reactions. Percentages of CD4 and CD8+ were calculated using a flow cytometer. Statistically significant decreased zinc levels, especially in the age group > or = 40 years, and increased C4, IgA, IgM, IgG and CD4+ levels were observed in hemodialysis patients. The prevalence of hypozincemia in hemodialysis patients was found to be 40%. A higher CD4+/CD8 ratio was also obtained in patients. We conclude that patients on maintenance hemodialysis for a short time exhibit zinc deficiency and disturbed immune response.

Oxidation of uric acid in rheumatoid arthritis: is allantoin a marker of oxidative stress?

Free radicals are implicated in many diseases including atherosclerosis, cancer and also in rheumatoid arthritis. Reaction of uric acid with free radicals, such as hydroxyl radical and hypochlorous acid (HOCl) results in allantoin production. In this study, we measured the serum allantoin levels, oxidation products of uric acid, as a marker of free radical generation in rheumatoid arthritis. Fasting blood samples were obtained from 21 rheumatoid patients and 15 healthy controls. In this study, the serum allantoin and uric acid levels were measured by a gas chromatography-mass spectrometry method and the ratios were calculated. The mean allantoin and uric acid levels and ratios in the patient group were 22.1 +/- 11.3, 280.5 +/- 65.0 and 8.0 +/- 3.7 microM, while in the control group they were 13.6 +/- 6.3, 278.3 +/- 53.6 and 4.9 +/- 2.1 microM, respectively. The effects of gender, age, menopausal status, duration of disease and medications on serum allantoin and uric acid levels of the patient and control groups were studied. Our results suggest that uric acid acts as a free radical scavenger and thus is converted to allantoin. Increased allantoin levels suggest the possible involvement of free radicals in rheumatoid arthritis.

The role of plasma thiol compounds and antioxidant vitamins in patients with cardiovascular diseases.

BACKGROUND: Increased levels of homocysteine (Hcy) and cysteine (Cys) are associated with risk of cardiovascular diseases (CVD). These thiol compounds can generate various free radicals and so cause endothelial dysfunction. Antioxidant vitamins are effective scavengers of reactive oxygen species (ROS) and prevent endothelial dysfunction. In this study, we investigated the plasma homocysteine, cysteine, vitamins E, C and A, and beta-carotene (BC) levels in cardiovascular patients to compare with controls. We also investigated whether there is a correlation between the plasma thiol compounds and antioxidant vitamins. METHODS: Blood samples were collected from 47 patients with cardiovascular disease (16 women and 31 men) and 21 healthy subjects (8 women and 13 men) in the overnight fasting state. Serum thiol compound and antioxidant vitamin levels were measured by high-pressure liquid chromatography (HPLC) methods. RESULTS: The plasma homocysteine and cysteine levels were significantly higher in patients than those of controls. While vitamin C (VC), vitamin A (VA) and beta-carotene levels were significantly lower in patients than in controls, vitamin E (VE) levels did not change in both groups. There is a positive correlation between homocysteine and cysteine levels (r=0.622, p=0.000) in all study population. We found that the plasma level of homocysteine was significantly correlated in negative manner with vitamins E and A levels (r=-0.260, p=0.033 and r=-0.255, p=0.036, respectively) of all study population. Plasma cysteine levels were negatively correlated with only vitamin C levels (r=-0.320, p=0.008) in all study populations. CONCLUSIONS: Our data suggest that Hcy and Cys are associated with cardiovascular disease and there is negative but weak correlation's between thiol compounds and antioxidant vitamins.