Pervin Vural

Antioxidant defence in recurrent abortion

Increased free radical activity has been implicated in the pathogenesis of recurrent abortion. This investigation was conducted to determine if changes in some parameters of the antioxidant system contribute to this condition. Plasma ascorbic acid, alpha-tocopherol, total thiols, ceruloplasmin, uric acid, albumin, and erythrocyte glutathione (GSH) were assayed in 25 nonpregnant (NP) healthy women, 25 normotensive pregnants (NTP), and 120 women with recurrent abortion. Recurrent aborters were divided into four subgroups according to the etiology: autoimmune (AUTO, n=25), luteal phase defect (LPD, n=25), anatomical defect (AD, n=20) and unexplained (UNEx, n=50). Plasma levels of ascorbic acid, alpha-tocopherol, and erythrocyte GSH were significantly decreased in AUTO, UNEx and LPD subgroups than those in two control groups and the AD group (ANOVA). Plasma thiols of UNEx and AUTO aborters were diminished according to controls and other abortion subgroups (ANOVA). Ceruloplasmin levels showed a decline in AUTO and UNEx subgroups when compared to controls, AD and LPD aborters (ANOVA). When UNEx, AUTO and LPD recurrent abortion subgroups were compared with each other (Students t-test) total thiols and erythrocyte GSH of UNEx and AUTO subgroups were diminished in comparison with LPD. We suggest that decreased concentrations of plasma ascorbic acid, alpha-tocopherol, total thiols and erythrocyte GSH in UNEx, AUTO and LPD reflect the increased oxidative stress, expressing a progress of the condition. Also, the imbalance between antioxidant defence and free radical activity is more evident in the AUTO subgroup. As a conclusion, although impaired antioxidant defence may be responsible for recurrent abortions, the recurrent abortions may also result in oxidative stress and depletion and weakness of antioxidant defence.

Tumor necrosis factor α, interleukin-6 and interleukin-10 polymorphisms in preeclampsia

Aim:  Preeclampsia (PE) is one of the most serious disorders of pregnancy. The imbalance between pro‐ and anti‐inflammatory cytokines may play a role in its etiology. The aim of the present study was to investigate whether cytokine gene polymorphism is associated with PE, and to evaluate the relationship between genotypes and clinical/laboratory manifestation of PE.

The combinations of TNFα -308 and IL-6 -174 or IL-10 -1082 genes polymorphisms suggest an association with susceptibility to sporadic late-onset Alzheimer's disease.

Objective –  Single nucleotide polymorphisms in the regulatory regions of the cytokine genes for tumor necrosis factor α (TNFα), interleukin (IL)‐6 and IL‐10 have been suggested to influence the risk of Alzheimer’s disease (AD) with conflicting results.

Plasma antioxidant defense in actinic keratosis and basal cell carcinoma

Reactive oxygen species and lipid peroxides have been implicated in the pathogenesis of a variety of diseases, particularly cancer. There may be an inverse correlation between lipid peroxidation and antioxidant defense mechanisms. The aim of this study was to investigate whether certain plasma antioxidants (ascorbic acid, α‐tocopherol, total thiol groups, ceruloplasmin, urate, albumin and erythrocyte glutathione) are altered in actinic keratosis (AK) and basal cell carcinoma (BCC).

Nitric oxide/endothelin-1 in preeclampsia

BACKGROUND Preeclampsia is characterized by vasospasm, multiple organ hypoperfusion and endothelial cell damage. Many of its signs and symptoms can be explained by an imbalance in the vasomotor tone-regulating factors, including nitric oxide (NO) and endothelin-1 (ET-1). METHODS Plasma samples of 59 women (20 healthy nonpregnant (NP), 20 normotensive pregnant (NTP) and 19 preeclamptic pregnant (PEP) women) were investigated by means of nitrite (NO(2)(-))/nitrate (NO(3)(-)) (two end products of nitric oxide metabolism) and endothelin-1 values. RESULTS PEP, when compared with NP and NTP, showed a significant increase in the plasma nitrite/nitrate and endothelin-1 concentrations. There was a weak but significant correlation between the nitrite/nitrate and endothelin-1 concentrations in the NP and NTP groups (r(1)=0.46, P<0.05, and r(2)=0.38, P<0.05, respectively) which probably revealed the balance between these vasoactive factors. In PEP, no significant correlation between nitrite/nitrate and endothelin-1 was found. Increased nitric oxide production could be the compensation against the vasoconstriction and hypertension in preeclampsia. CONCLUSIONS A lack of correlation between nitrite/nitrate and endothelin-1 probably indicates that in preeclampsia, a primary defense mechanism of the compensatory nitric oxide may be lost.

Tumor necrosis factor α (-308), interleukin-6 (-174) and interleukin-10 (-1082) gene polymorphisms in polycystic ovary syndrome.

OBJECTIVE The imbalance between pro- and anti-inflammatory cytokines and polymorphism of cytokine genes may play a role in the etiology of the polycystic ovary syndrome (PCOS). The aim of this study was to investigate the association of polymorphisms of TNFalpha, IL-6 and IL-10 genes with the occurrence and the clinical/laboratory characteristics of PCOS in the Turkish population. STUDY DESIGN Single nucleotide polymorphisms (SNPs) of TNFalpha (-308 G/A), IL-6 (-174 G/C), IL-10 (-1082 G/A) genes in DNA from peripheral blood leukocytes of 97 PCOS patients and 95 healthy control women were investigated. RESULTS There is a tendency toward lower frequency of the IL-6 CC genotype and C allele among PCOS women compared with healthy controls although the difference did not reach a significant level. No notable differences were observed in allele or genotype frequencies for TNFalpha and IL-10 genes between groups. The concomitant presence of wild homozygous TNFalpha genotype together with mutant IL-6 C allele has a protective effect against PCOS with an OR=0.45 (95% CI=0.23-0.86). While TNFalpha (-308) and IL-10 (-1082) genotypes did not influence clinical/laboratory parameters in PCOS, IL-6 (-174) CC or pooled CG+CC genotypes have lower glucose, insulin, HOMA, cholesterol, triglyceride, and LDL-C, and higher GIR and HDL-C values than GG genotypes. CONCLUSIONS We suggest that the IL-6 promoter region polymorphism may be related to occurrence and metabolic abnormalities seen in PCOS in the Turkish population. However, more studies with larger sample size are necessary to support our findings in other populations before any statement can be made about the relationship between PCOS and cytokine polymorphism.

Acute-phase reactans in Hashimoto thyroiditis

Hashimoto thyroiditis (HT) is one of the autoimmune diseases of the thyroid gland. It is characterized by diffuse lymphocytic infiltration of the thyroid gland and the elevated levels of the serum anti-thyroid antibodies. Recently Hashimoto thyroiditis has been proposed as a systemic disorder. Acute-phase reactans have been implicated for their involvement as pro-inflammatory molecules in various inflammatory diseases. The aim of the present study was to examine the blood concentrations of acute-phase proteins, namely C-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen in the patients with Hashimoto thyroiditis. Two groups were enrolled: study group consisting from euthyroid patients with HT (n=30), and healthy control subjects (n=30). Blood samples were obtained from all the patients and control subjects and were analyzed for serum CRP, SAA, fibrinogen, and ESR. Mean ESR was found to be higher in HT patients than control group (p=0.024). The mean fibrinogen and SAA values in HT were also significantly higher than that of the control group (p=0.03, p=0.002). We therefore suggest that a low-grade systemic inflammation may exist in HT patients even if they were euthyroid.

The relationship between transforming growth factor-β1, vascular endothelial growth factor, nitric oxide and Hashimoto's thyroiditis

BACKGROUND Hashimotos thyroiditis (HT) is one of the autoimmune disorders of the thyroid gland. The pathogenesis of HT has not been clearly understood. This study was designed to investigate plasma transforming growth factor-beta1 (TGF-beta1), vascular endothelial growth factor (VEGF), and nitrate/nitrite (NOx - two end products of nitric oxide [NO] metabolism) in HT. METHODS Forty patients diagnosed HT and 40 age- and sex-matched healthy controls were included in the study. TGF-beta1 and VEGF levels were measured by ELISA, NOx levels were measured spectrophotometrically. RESULTS Plasma TGF-beta1 and VEGF were decreased, and NOx increased in HT patients in comparison with controls. There was a significant correlation between TGF-beta1 and VEGF, and weak but significant correlation between TGF-beta1 and NOx in HT. CONCLUSION This study indicates that TGF-beta1, VEGF and NO probably have a role in the pathogenesis of Hashimotos thyroiditis, and development of autoimmunity. Clearly, further studies are necessary to establish the exact mechanism of TGF-beta1, VEGF and NO interaction in Hashimotos thyroiditis.

The combination of ınterleukin-10 − 1082 and tumor necrosis factor α − 308 or ınterleukin-6 − 174 genes polymorphisms suggests an association with susceptibility to Hashimoto's thyroiditis

BACKGROUND The etiopathogenesis of Hashimotos thyroiditis (HT) has not been clearly elucidated although the role of chronical inflammation and endothelial dysfunction has been established. The imbalance between pro- and anti-inflammatory cytokines may play a role in the etiology. The aim of the present study was to investigate whether cytokine gene polymorphisms are associated with HT, and to evaluate the relationship between genotypes and clinical/laboratory manifestation of HT. METHODS Tumor necrosis factor α (TNFα) G-308A (rs 1800629), interleukin-6 (IL-6) G-174C (rs 1800795) and IL-10 G-1082A (rs 1800896) single nucleotide polymorphisms (SNPs) in DNA from peripheral blood leukocytes of 190 patients with HT and 231 healthy controls were investigated by real-time PCR combined with melting curve analysis using fluorescence-labeled hybridization probes. RESULTS There was no notable risk for HT afflicted by TNFα -308, IL-6 -174 and IL-10 -1082 polymorphisms alone. However, carriers of variant alleles of both IL-10 -1082 and TNFα -308 polymorphisms had four-fold times higher risk for HT in comparison with non-carriers. Additionally, concomitant presence of both mutant IL-10 -1082 A and IL-6 -174 C alleles raised three-fold the HT risk. CONCLUSION Our results suggest that the combined effects of TNFα -308, IL-6 -174 and IL-10 -1082 variant alleles may be more decisive to induce functional differences and modify the risk for HT.

Nitric oxide and endothelin-1,2 in actinic keratosis and basal cell carcinoma: changes in nitric oxide/endothelin ratio.

Abstract