Cemil Akgül

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.

Effects of menopause and tibolone on antioxidants in postmenopausal women

Background: Oxidative stress has been implicated in the pathogenesis of ageing and menopause, and can arise through the increased production of lipid peroxides and/or a deficiency of antioxidant defence. Aim: To investigate the effects of the menopause and tibolone treatment (2.5 mg/day for six months) on plasma antioxidants and lipid peroxidation. Methods: Plasma concentrations of ascorbic acid, α-tocopherol, total thiol groups, caeruloplasmin, erythrocyte glutathione (GSH) and malondialdehyde (MDA) were measured in 24 postmenopausal and 24 premenopausal healthy women. Results: Data analysis indicates a significant decrease in plasma ascorbic acid, α-tocopherol, total thiol groups, caeruloplasmin, erythrocyte GSH and a significant increase in lipid peroxides (expressed as MDA concentrations) in postmenopausal women. There was no significant difference between control and study groups in the mean plasma caeruloplasmin concentrations. It was found that there is a significant increase in α-tocopherol and significant decrease in lipid peroxide concentrations in postmenopausal after tibolone treatment. Conclusions: The menopause is associated with an increase in oxidative stress and a decrease of some antioxidants, such as ascorbic acid, α-tocopherol, total thiols and erythrocyte GSH. Tibolone treatment leads to a decrease in concentrations of plasma lipid peroxide, probably by stimulating direct and indirect mechanisms of tocopherol regeneration and increasing plasma concentrations of vitamin E. However, due to the relatively small numbers involved this study can be regarded as a pilot. Further studies performed on a larger scale are necessary to establish the exact mechanisms of tibolone in inhibiting oxidative stress in postmenopausal women.

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.

Hormone replacement therapy and urinary prostaglandins in postmenopausal women

The objective of the study was to observe the effects of hormone replacement therapy upon urinary prostaglandin E2 and prostaglandin F2 alpha levels in postmenopausal patients. A total number of 55 women were enrolled in this study and 15 premenopausal (PreM) healthy subjects constitute the control group. A total of 40 patients at least 12 months after their natural menopause were divided into two groups: 15 of them was not medicated hormone replacement therapy (which composed NRHRT group) while 25 of the rest, received conjugated estrogen (Premarin) 0.625 mg/day orally plus medroxyprogesterone acetate (Farlutal) 10 mg/day orally built up the RHRT group. PGE2 and PGF2 alpha levels were measured with PGE2 [125I] and PGF2 alpha [3H] RIA kits. Statistical significance was analyzed by Students t-test for impaired data. NRHRT and RHRT patients had had increased urinary PGE2 levels when compared with PreM (P < 0.001). HRT caused a significant decrease in PGE2 levels in menopausal women (P < 0.001). Urinary PGF2 alpha values of NRHRT and RHRT were significantly lower (P < 0.001) in comparison with PreM group. There was no difference in PGF2 alpha values between two postmenopausal groups. HRT given to postmenopausal patients might have a positive impact on prostaglandins and therefore on bone turnover in a series of various mechanisms.

Urinary PGE2 and PGF2α Levels and Renal Functions in Preeclampsia

The role of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) in the pathogenesis of hypertension and altered renal functions, which are the main symptoms of preeclampsia, has gained importance. Serum and urine samples of 59 women (24 preeclamptic pregnant (PEP), 20 normotensive pregnant (NTP) and 15 nonpregnant) were investigated by means of prostaglandin levels and urea, creatinine and creatinine clearance values. PEP patients, when compared with NTP patients, show a significant decrease in PGE2 and PGF2α levels (p < 0.01 and p < 0.05, respectively) accompanied by changes in some parameters of renal function such as serum urea, creatinine and creatinine clearance. Although disorders in prostaglandin levels may be responsible for some renal pathologic changes, renal functional and morphologic alterations may also result in abnormal prostaglandin activity.

Effects of tibolone on thromboxane B2 levels in postmenopausal women

This study was carried out in 16 premenopausal (control) and 24 postmenopausal women (study group) to investigate the effect of menopause and tibolone treatment (2.5 mg/day for 6 months) on plasma thromboxane B2 (TxB2), a well-known vasoconstrictor and stimulator of platelet aggregation. The TxB2 levels were measured using [125I] RIA kit. Statistical significance was analyzed by Student’s t test for paired and unpaired data, and Pearson’s correlation analysis. Plasma TxB2 concentrations of postmenopausal women were higher than those of premenopausal women. Tibolone treatment decreased plasma TxB2 in postmenopausal women. There was no correlation between TxB2 and blood pressure and heart rate. It was concluded that tibolone, decreasing the plasma concentrations of TxB2, might have beneficial effects on prostaglandin metabolism and thus reduce the risk of cardiovascular disease.

Impact of Calcitonin on Urinary Excretion of Prostaglandins during Menopause

The aim of this study was to investigate the effects of calcitonin as an antiresorptive agent in postmenopausal osteoporosis in prostaglandin metabolism. Urinary prostaglandin E2 (PGE2) concentrations were determined by PGE2 (125I) RIA kit in a total number of 37 patients in postmenopause; 27 in study group with established osteoporosis (WEO) and 10 in another group without osteoporosis (WO). An additional group of 12 patients in the premenopausal period were selected as controls (PreM). Data were given as mean ± SD and statistical analysis was performed by Student’s t test for paired and unpaired values. A significant decrease in urinary PGE2 concentrations was observed in WEO (7.91 ± 3.08 vs. 3.79 ± 3.01 ng/l) (p < 0.001), WO (9.06 ± 6.76 vs. 6.06 ± 3.90 ng/l) (p < 0.05) and PreM (7.14 ± 1.68 vs. 5.16 ± 1.91 ng/l) (p < 0.01). As a conclusion, calcitonin seems to exert a negative effect on prostaglandin metabolism resulting in reduced new prostaglandin formation.