CIRCULATING MIR-132, MIR-146A, MIR-222, AND MIR-320 EXPRESSION IN DIFFERENTIAL DIAGNOSIS OF WOMEN WITH POLYCYSTIC OVARY SYNDROME.

Purpose: The aim of the study was to investigate whether the circulating miR-132, miR-146a, miR-222, and miR-320 levels are used in the differential diagnosis of women with polycystic ovary syndrome (PCOS) and healthy women. Methods: This prospective case-control study included 50 women with PCOS and age- and body mass index- matched 50 healthy controls. The hormone and lipid profiles, levels of microRNAs (miRNAs), and parameters of carbohydrate metabolism were measured. Results: Expression levels of miRNAs were assessed using the two-step quantitative real-time polymerase chain reaction. Circulating miR-132, miR-146a and miR-222 levels were significantly downregulated in the PCOS group compared with the control group. The miR-320 levels did not differ between the two groups. Free testosterone was negatively correlated with miR-132, miR-146a and miR-222. Insulin was negatively correlated with miR-132 and miR-146a. Conclusions: The results of the study revealed that miRNA expression, may suggest a possible distinction between healthy women and PCOS patients. miR-132, miR-146a, and miR-222 may have key functions in the pathogenesis of PCOS.

The impact of TFPI on coronary atherosclerotic burden.

OBJECTIVES: We aimed to associate a coronary artery disease (CAD) presence and severity with endothelial dysfunction (ED), carotid intima media thickness (CIMT) and Tissue Factor Pathway Inhibitor (TFPI). BACKGROUND: ED has a central role in atherosclerosis. CIMT and TFPI activity are also related with atherosclerosis and CAD. METHODS: In our prospective observational study, 50 patients had CAD and 30 had normal coronary arteries. Endothelial function was evaluated by endothelium-dependent flow-mediated dilatation (FMD) and nitroglycerine-mediated dilatation (NMD) measurements. CIMT and Serum TFPI levels were also measured. RESULTS: TFPI was a statistically significant determinant between the two groups with an increased level in CAD (+) group (84.9 ± 19.3 vs 70.2 ± 14.7, p = 0.001). There was a positive correlation between CIMT and Gensini (r = 0.34, p = 0.014). There was a strong negative correlation between Gensini and FMD-NMD, statistically significant (FMD: r = -0.715, p < 0.001; NMD: r = -0.718, p < 0.001). CONCLUSION: We observed that ED, increased CIMT and TFPI levels were associated with CAD. Additionally, increased CIMT measurements and decreased FMD and NMD values had a positive correlation with GSS (Tab. 4, Fig. 6, Ref. 50).

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.

Effects of peritoneal-and hemodialysis on levels of plasma protein and lipid oxidation markers in diabetic patients.

AIM: The aim of this paper was to evaluate the effects of dialysis procedures on oxidative stress in diabetic patients. METHODS: The study was performed on 15 non-diabetic hemodialysis (HD) patients, 30 non-diabetic perinoteal dialysis (PD) patients, 18 diabetic HD patients (DHD), 15 diabetic PD patients (DPD), and 20 healthy controls. Plasma thiobarbituric acid reactive substances (TBARS), protein carbonyl (PCO), and oxidized LDL (oxLDL) were determined as oxidative stress markers. Plasma thiol (P-SH), erythrocyte glutathione (GSH) levels, and serum paraoxonase (PON1) activities were measured as antioxidants. RESULTS: HD patients have significantly higher oxLDL, TBARS and PCO levels and significantly lower P-SH levels than PD patients. DHD patients have significantly higher PCO levels and PON1 activities and significantly lower GSH levels than non-diabetic HD patients. There was no any difference in oxidative stress parameters between DPD and non-diabetic PD patients. CONCLUSION: Oxidative stress is exacerbated by HD in diabetic patients. Treatment strategy with antioxidants in dialysis patients may be associated with a worsened survival.

Effects of atorvastatin therapy on protein oxidation and oxidative DNA damage in hypercholesterolemic rabbits.

OBJECTIVE: Our aim was to clarify the effects of hypercholesterolemic diet and administeration of atorvastatin on lipid peroxidation, protein oxidation and oxidative DNA damage in male New Zealand white rabbits. METHODS: We determined malondialdehyde (MDA), protein carbonyl (PCO) and total thiol (T-SH) levels in plasma and liver tissue, glutathione (GSH) levels in erythrocyte and liver tissue, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in plasma. Twenty rabbits were randomly divided into two groups and fed with a high-cholesterol diet (fortified with 1% cholesterol) for 4 weeks. Such rabbits were subjected to either (Group 1) a high-cholesterol diet non-supplemented with atorvastatin (n=10) or (Group 2) a high-cholesterol diet supplemented with atorvastatin (0.3mg atorvastatin per day/kg body weight) for 4 weeks (n=10). A control group (n=5) (Group 3) was fed a cholesterol free diet for 4 weeks. Colorimetric methods were used to determine the level of the oxidative stress markers, except 8-OHdG, which was measured by ELISA. RESULTS: Rabbits were fed with the high-cholesterol diet alone (Group 1) showed higher levels of lipid profile and oxidative protein and DNA damage than compared with dose of the control group (Group 3). Atorvastatin therapy has substantially beneficial effects on oxidative protein and DNA damage in hypercholesterolemic rabbits. CONCLUSIONS: The current findings will, we hope, lead to a new insight into the pathogenesis of atherosclerosis. On the other hand inhibition of protein oxidation and DNA oxidation in the plasma by atorvastatin may be one of the pleiotropic effects of statins, and thus the underlying mechanism needs to be further clarifications.

Total acid soluble and insoluble carnitine levels in human brain tumors.

Carnitine has two main functions, i.e., transporting long-chain fatty acids into the mitochondrial matrix for beta-oxidation to provide cellular energy and modulating the rise in intramitochondrial acyl-CoA/CoA ratio, which relieves the inhibition of many intramitochondrial enzymes involving glucose and amino acid catabolism. The present study examined the acid soluble carnitine (ASCAR) acid insoluble carnitine (AICAR) and total carnitine (TCAR) concentrations of 50 human brain tumor tissues and 11 normal brain tissues. The ASCAR levels significantly higher in gliomas and meningiomas than brain, however similar to brain in metastatic adenocarcinomas. AICAR levels were lower than brain in all tumors with the exception of a medullablastoma. TCAR levels were similar to brain in all tumor types. Decreased AICAR levels may be due to increased utilization of lipids or enhanced phospholipid and cholesterol synthesis which is need for increased membrane synthesis or formation of eicosanoids. Also decreased concentrations may be a reflection of camitine and its acylesters role in preserving the physiologic membrane structure function from oxidative damage.

A preliminary study on IL4 levels in extrinsic atopic asthmatic children.

Interleukin 4, (IL4) known as a lymphokine secreted by type II helper T-cells, is thought to regulate IgG and IgE secretions. Therefore, elevated IL4 levels are expected in atopic allergic disease and parasitoses. The purpose of this study was to determine IL 4 levels in allergic asthmatic children. In 50 extrinsic atopic children (19 females, 31 males, mean age 8 +/- 4), IgE and IL 4 were found to be 469 +/- 296 U/L and 0.318 +/- 0.09 ng/ml, respectively. In seven control cases, IgE and IL4 levels were 62 +/- 25 and 0.106 +/- 0.017, respectively. Comparison of the two groups disclosed statistically significant differences in IL4 and IgE levels, suggesting the ability of IL4 to augment IgE production.