Paraoxonase, oxidized low density lipoprotein, monocyte chemoattractant protein-1 and adhesion molecules are associated with macrovascular complications in patients with type 2 diabetes mellitus.

AIM: The aim of this paper was to evaluate the association between blood glucose, oxidative stress, inflammation, endothelial dysfunction and paraoxonase activity as contributors to the accelerated atherosclerosis seen in type 2 diabetic patients. METHODS: Plasma malondialdehyde (MDA), oxidized LDL (oxLDL), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cellular adhesion molecule-1 (VCAM-1) levels and paraoxonase-1 (PON1) activity were measured in sixty type 2 diabetic patients, 30 of whom had macrovascular complications, and 30 controls. RESULTS: Diabetics with macrovascular complications had higher levels of MDA, oxLDL, MCP-1, ICAM-1, VCAM-1 than those without, and the difference was significant for all molecules except for ICAM-1. PON1 activity and ApoA1 levels of the controls were significantly higher than that of the patients, while PON1 activity and ApoA1 levels in the patients with macrovascular complications were significantly lower than that in patients without. Ambient plasma glucose concentration showed a significant positive association with plasma MDA, oxLDL, MCP-1, and VCAM, and a significant inverse association with PON1 and ApoA1 in diabetic patients. A significant positive correlation between oxLDL and MDA, a negative correlation between oxLDL and PON1; a significant inverse association between MDA and PON1; a positive correlation between MDA and MCP-1 and VCAM while a negative correlation between PON1 and MCP-1 and VCAM were detected in patients. CONCLUSION: Hyperglycemia might play a significant role in generating increased oxidative stress, and decreased PON1 activity, resulting in elevated oxLDL, MCP-1 and VCAM levels. This might be one of the causal pathogenic factors initiating accelerated atherosclerosis in patients with type 2 diabetes mellitus. The implication of these findings are unclear and therefore further studies are required.

Comparison of maternal and umbilical cord blood soluble lectin-like oxidized low-density lipoprotein receptor 1 levels in early- and late-onset preeclampsia.

BACKGROUND: The main purpose of this study was to determine the maternal and umbilical cord blood oxidized LDL (oxLDL) and soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) levels in early- and late-onset preeclampsia (PE). MATERIALS AND METHODS: A case-control study was conducted in pregnant women with early-onset (before 34 weeks' gestation n = 19) and late-onset (after 34 weeks' gestation n = 22) PE compared to healthy normotensive pregnant controls (n = 44). Groups were compared for the maternal and umbilical cord plasma oxLDL and serum sLOX-1 levels. RESULTS: The mean maternal and umbilical cord serum sLOX-1 and plasma oxLDL levels were significantly increased in early- and late-onset PE compared to controls (p < 0.001). When early- and late-onset PE women were compared with serum sLOX-1 levels, the increase was more pronounced in early PE (p < 0.001). However, same comparison is not statistically significant in cord blood for oxLDL where as it is significantly higher in maternal blood for oxLDL in early-onset PE group. Maternal and cord blood oxLDL and sLOX-1 levels are positively correlated with each other; however, they are negatively correlated with fetal weight and gestational age. CONCLUSIONS: According to our results, maternal and umbilical cord blood levels of oxLDL and sLOX-1 were higher in preeclamptic pregnant. Thus, for the first time it has been shown that oxLDL and sLOX-1 levels were higher in fetal circulation as well as plasma of preeclamptic pregnant. However, sLOX-1 levels seem to be more implying than oxLDL for the differentiation of early and late preeclampsia.

Changes in oxidative stress parameters and antioxidant status in lung cancer: Western blot analysis of nitrotyrosine and protein carbonyls content.

INTRODUCTION: The source of many diseases, including tumors, lies in an increased generation of reactive oxygen species resulting in oxidative stress. We investigated the relationships between advanced oxidation protein products (AOPPs), nitrotyrosine (NT), protein carbonyls (PCO) content, and the prooxidant-antioxidant balance (PAB) in patients with lung cancer. METHODS: A total of 14 age-matched healthy controls, 14 subjects with non-lung cancer pulmonary disease, and 41 patients with lung cancer were included in this study. Spectrophotometry was used to examine plasma AOPP, serum FRAP, and PAB, while serum PCO and NT were assessed with western blot analysis. RESULTS: A significant difference in AOPP levels were found between patients and controls (p < 0.01). Also, there was a highly significant difference in NT levels between patients and controls (p < 0.001). PAB showed negative correlation with albumin (r = -0.340, p = 0.011) and positive correlation with CRP (r = 0.342, p = 0.011). AOPP, albumin, gender, and smoking were the significant independent variables found by backward stepwise multiple logistic regression (MLR) analysis method. MLR analysis revealed that AOPP was the variable that had a significant effect on lung cancer [(p = 0.006, OR = 1.074, (95% CI) (1.020-1.131)]. CONCLUSIONS: The use of non-invasive diagnostic biochemical parameters would represent a very important contribution to our diagnostic armamentarium in lung cancer, considering the high incidence of this deadly disease. In this regard, AOPP and NT levels have appeared to play a prominent role, although further studies are certainly warranted.

Serum thymidine kinase 1 activity in solid tumor (breast and colorectal cancer) patients treated with adjuvant chemotherapy.

BACKGROUND: The aim of this study was to evaluate the changing of TK1 (where TK is thymidine kinase) activity before and after adjuvant chemotherapy in patients with breast and colorectal cancer. METHODS: The study included 16 breast cancer, 25 colorectal cancer, and 38 healthy volunteers as the control group. Blood samples were taken twice from each patient; first at the beginning of the chemotherapy and second after six cycles of chemotherapy. TK1 activity was measured enzyme immunoassay method. RESULTS: The mean TK1 activity in the breast and colorectal cancer was significantly higher than the controls. TK1 activity in the colorectal cancer was higher than the breast cancer but this difference was not significant. TK1 activity after six doses of chemotherapy was lower than baseline TK1 activity before the start of chemotherapy in breast and colorectal cancer. TK1 activity was positively correlated with CA15-3, before and after chemotherapy in patients with breast cancer. TK1 activity in the colorectal cancer was also positively correlated with CA19-9, before and after chemotherapy. The values for the cutoff point, sensitivity, specificity, and the area under curve were determined for TK1 as >44.36 Du/L, 68.29%, 100% and 0.819, respectively in all subjects. CONCLUSION: Our results showed that serum TK1 activity in patients with breast and colorectal cancer was significantly higher than that of the healthy controls. Moreover, after the completion of chemotherapy the values were lower than baseline. Pretreatment TK1 activity should be considered as a useful marker for assessment tumor cell proliferation in breast and colorectal cancer. Further work is needed to understand TK1 activity better in large populations of patients with solid tumor.

The relationship between ischemia modified albumin and oxidative stress parameters in patients with cardiac syndrome X.

BACKGROUND: The objective of this study was to evaluate the serum levels of ischemia modified albumin and oxidative stress parameters in patients with cardiac syndrome X. METHODS: A total of 61 patients, composed of 32 consecutive patients (24 female, 8 male, average age: 47.63 +/- 9.49 years) diagnosed with cardiac syndrome X by coronary angiography (initially performed following the identification of ischemia by exercise stress test or myocardial perfusion scintigraphy) and a control group of 29 consecutive patients (15 female, 14 male, average age: 49.59 +/- 11.68 years) with similar features without cardiac syndrome X were included in the study. The levels of the ischemia modified albumin (IMA), ferric reducing antioxidant power (FRAP), prooxidant-antioxidant balance (PAB), and advanced protein oxidation products (AOPP) were determined by colorimetric methods. RESULTS: Patients have significantly higher PAB, AOPP, and IMA levels in the patient group than in the control group (p < 0.01, p < 0.001, and p < 0.02, respectively). Also, serum triglyceride (p < 0.005) and hs-CRP (p < 0.0001) levels were significantly higher in the patient group (p < 0.01, p < 0.001, and p < 0.02, respectively). We found that there was a significant correlation between hs-CRP, plasma PAB (r: 0.258; p < 0.05), AOPP (r: 0.459; p < 0.001), and triglyceride levels (r: 0.404; p < 0.01). Plasma AOPP levels were also significantly positive correlated with triglyceride levels (r: 0.463; p < 0.001). In addition, during the correlation analysis performed on the patient group, a positive correlation was observed between the levels of IMA with the levels of plasma PAB and plasma AOPP (r: 0,994; p < 0.01 and r: 0.857; p < 0.05, respectively) In a multiple linear regression analysis, AOPP levels were significantly related with hs-CRP and triglyceride (R2: 0.380, p < 0.0001 and p < 0.05). Simple linear regression analysis was performed between plasma PAB (as dependent variable) and hs-CRP levels. Plasma PAB levels were related with hs-CRP (R2: 0.258, p < 0.05). Using the receiver-operator characteristic (ROC) curve, the best cut-off values for predicting cardiac syndrome X of PAD, AOPP, IMA, and hs-CRP levels were 88.1 arbitrary units, 68.5 kloramin T micromol/L, 7.17 U/mL, and 1.09 mg/dL, respectively. CONCLUSIONS: Based on the results of our study, the increase in oxidative stress during cardiac syndrome X appears to be related to elevated levels of IMA. Treatment modalities that decrease oxidative stress might be beneficial for the treatment of cardiac syndrome X.

Evaluation of serum paraoxonase and arylesterase activities in subjects with asthma and chronic obstructive lung disease.

BACKGROUND: Asthma and chronic obstructive lung disease (COPD) are characterised by airway inflammation. Paraoxonasel (PON1) and arylesterase (AE) enzymes have the ability to protect HDL from oxidation and may have antiatherogenic, antioxidant, and antiinflammatory features. We carried out a study to assess if there is a difference between PON1 and AE activities and biochemical values between asthmatics and COPD patients and if there is a difference between comorbid or pure COPD patients. METHODS: 40 asthmatics, 20 pure COPD, 20 comorbid COPD patients, and 20 healthy controls were included. We excluded patients with hypertension, metabolic syndrome, diabetes mellitus, thyroid, renal, hepatic, rheumatic, cardiac, cerebrovascular, malignant, and infectious diseases to establish the asthma and pure COPD groups. Patients using drugs which could affect PON1 and AE were excluded in these groups. There were 11 hypertensive, 5 diabetic, and 4 cardiac patients in the comorbid COPD group. PON1 and AE activities were measured spectrophotometrically. RESULTS: Mean age was higher and male gender was more prevalant in COPD than other groups. Fasting blood glucose, LDL-cholesterol, triglyceride, leucocyte counts, erythrocyte sedimentation rate, and hs-CRP levels were higher in COPD patients. Although PON1 and AE were lower in patients than controls, no difference was found between the asthma and COPD groups, nor between pure and comorbid COPD patients. CONCLUSIONS: Although asthma and COPD are two different conditions PON1 and AE activities cannot be markers of differantial diagnosis as they overlap. Comorbid COPD patients may have similar enzyme levels because of the drugs such as statins and aspirin.

The role of feed regulating peptides on weight loss in patients with pulmonary tuberculosis.

PURPOSE: Malnutrition is a prominent feature of tuberculosis (TB). The aim of our study was to explore the function of plasma regulatory proteins in pulmonary TB and to investigate the relationship between these parameters and loss of body weight. METHODS: Plasma levels of fasting insulin, leptin, ghrelin, adiponectin and orexin-A were measured in 23 pulmonary TB patients, 39 patients with pulmonary sarcoidosis, 22 patients with different diffuse interstitial lung diseases and 21 healthy patients serving as controls. RESULT: Plasma leptin (p<0.001) and orexin-A (p<0.01) levels were significantly decreased in TB patients compared with those of the other study subjects. TB patients also had higher levels of plasma ghrelin compared with those of the other study subjects, while sarcoidosis patients had higher plasma adiponectin levels than the other study subjects. Glucose levels were similar in all groups, yet, insulin and Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR) levels were significantly higher in the TB group compared to the other study groups. There was no correlation between leptin, ghrelin, adiponectin and orexin-A and other parameters. CONCLUSIONS: These data suggest that leptin and orexin-A levels have effects on weight loss in patients with pulmonary tuberculosis. Particularly, leptin may play a role in the early immune response to pulmonary TB and prolonged inflammation may further suppress leptin production. Measurement of HOMA-IR can indeed be used as a marker for the risk of activated TB. Further clinical studies are needed to better understand the role of feed regulating proteins in pulmonary tuberculosis.