Sevgi Yardim-Akaydin

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 μM, while in the control group they were 13.6±6.3, 278.3±53.6 and 4.9±2.1 μM, 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.

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 SaO2 (r = 0.513, p < 0.002) and lowest SaO2 (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 ≥ 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.

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

Abstract Background: Behçets disease is a multysystemic 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 Behçets disease, possible association of homocysteine with nitric oxide and neopterin levels, and to characterize the differences between patients with Behçets disease and those with recurrent aphthous stomatitis in terms of these parameters compared with healthy controls. Methods: A total of 23 patients with active Behçets 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 μmol/L) and lower nitric oxide (41.5±10.9 μmol/L) and neopterin (6.4±1.0 nmol/L) levels were observed in patients with Behçets disease compared with healthy controls (10.7±2.0 μmol/L, 49.7±16.2 μmol/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 Behçets disease (r=0.975, p<0.005). Conclusions: In contrast to recurrent aphthous stomatitis, there is a higher prevalence of hyperhomocysteinemia in Behcets disease. Homocysteine may have deleterious effects on the pathology of Behcets disease by decreasing nitric oxide levels and interfering with the immune system. Clin Chem Lab Med 2007;45:73–7.

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

Abstract 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, β-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 β-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. Clin Chem Lab Med 2008;46:107–12.

Evaluation of allantoin levels as a new marker of oxidative stress in Behçet's disease.

The increased production of reactive oxygen species (ROS) from activated neutrophils in Behçets disease (BD) and recurrent aphthous stomatitis (RAS) may result in increased oxidative stress. Uric acid can react rapidly with neutrophil‐derived ROS to form allantoin. The purpose of the study was to evaluate the serum levels of allantoin as a new marker of oxidative stress in BD compared with malondialdehyde (MDA) levels as a well‐known marker. Blood samples were obtained from 23 BD patients, 22 RAS patients as positive controls, and 21 healthy controls. When compared to the healthy controls, we found higher allantoin and MDA levels in the BD patients and higher MDA levels in the RAS patients. Serum ascorbic acid levels in the BD patients were significantly lower than in the controls. Increased allantoin and MDA levels suggest the possible involvement of free radicals in BD. As allantoin is only a product of uric acid oxidation by reactive oxygen and nitrogen species, it may also be used as a marker of oxidative stress in BD.

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.

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.

Increased tryptophan degradation in patients with bronchus carcinoma

Expression of tryptophan-degrading enzyme indoleamine (2,3)-dioxygenase in tumour tissue is proposed to represent an important tumour immunoescape mechanism. To further investigate the potential role of activated indoleamine (2,3)-dioxygenase in bronchus carcinoma, we examined serum tryptophan and kynurenine concentrations in nine patients with small cell lung cancer and in 27 patients with non-small cell lung cancer. Tryptophan metabolic changes were compared with markers of inflammation and immune activation namely C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and neopterin. Compared with controls, patients presented with lower tryptophan concentrations (P < 0.01) and with higher serum kynurenine to tryptophan ratios (P < 0.01), an index of tryptophan degradation. Also ESR and CRP and neopterin concentrations were increased in the patients (all P < 0.001), and there was a weak correlation between kynurenine to tryptophan ratio and ESR, CRP and neopterin concentrations. We conclude that in the majority of patients with non-small cell lung cancer and small cell lung cancer, enhanced tryptophan degradation can be observed. It seems to relate to an inflammatory response and may reflect activation of indoleamine (2,3)-dioxygenase at the tumour site. The capacity of the tumour to escape normal host immune defence may be influenced by tryptophan degradation. Results of this pilot study deserve further confirmation.

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

PurposeThe 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.MethodsThese variables were measured in 28 uncomplicated pregnant women at first, second and third trimesters and in 19 nonpregnant women.ResultsThe 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.ConclusionThis 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 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 mol/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.