Hypoxia-inducible factor-1α, hepcidin and interleukin-6 levels in pregnancies with preterm labour.

The aim of the study was to investigate whether serum hypoxia-inducible factor-1alpha (HIF-1α), hepcidin and interleukin-6 (IL-6) concentrations differed between threatened preterm labour (TPL) and uncomplicated pregnancies. This study was conducted on 54 women with TDL pregnancies and 26 healthy pregnant women. The TPL group was further divided into two subgroups according to the gestational age at delivery. Patients who gave birth within 48-72 h after the hospitalisation were referred to as preterm delivery (PD) and who gave birth at ≥37 weeks were referred to as term delivery (TD). Maternal levels of serum HIF-1α, hepcidin and IL-6 were measured with the use of enzyme-linked immunosorbent assay kits. The mean maternal serum HIF-1α, hepcidin and IL-6 levels of PD were significantly higher than TD (p < .001*) and control group (p < .001*). The mean maternal serum HIF-1α and hepcidin levels of TD were no significantly higher than the control group (p=.058, p = .064). The mean maternal serum IL-6 level of TD was significantly higher than the control group (p < .001*). A negative correlation was found between serum concentration of HIF1α, hepcidin, IL-6 with the gestational week of delivery (r = -0.421, p < .01* for HIF-1α; r = -0.578, p < .01* for hepcidin and r = -0.435, p < .01* for IL-6). High levels of HIF-1α, hepcidin and IL-6 may have potential to be used as biomarkers for the differentiation of PD and TD.Impact statementWhat is already known on this subject? It is known that hypoxia-inducible factor-1alpha (HIF-1α) is a hypoxia marker and hepcidin and interleukin-6 (IL-6) increase in inflammation. Our study is the comparison of maternal serum HIF-1α, hepcidin and IL-6 levels between the TPL group (TD and PD) and healthy control group.What the results of this study add? The present study demonstrates that serum HIF-1α, hepcidin and IL-6 levels were significantly higher in TPD group than uncomplicated group. The mean maternal serum HIF-1α and hepcidin levels of TD were no significantly higher than the control group.What the implications are of these findings for clinical practice and/or further research? High levels of HIF-1α, hepcidin and IL-6 may be biomarkers in the determination of true preterm labour within the TPL group.

Comparison of antagonist mild and long agonist protocols in terms of follicular fluid total antioxidant capacity.

OBJECTIVE: A high dose of prolonged gonadotropins can yield higher numbers of oocytes and embryos. The high dose or prolonged regimens can be associated with ovarian hyperstimulation syndrome (OHSS), multiple gestations, emotional stress, economical burden and treatment dropout. In mild stimulation lower doses and shorter duration times of gonadotropin are used in contrast to the conventional long stimulation protocol in IVF. It has been proposed that supraphysiologic levels of hormones may adversely affect endometrium and oocyte/embryo. Also it has been proposed that oxidative stress (OS) may alter ovarian hormone dynamics and could be further affected by additional exogenous hormonal stimulation. Therefore our aim was to compare follicular fluid total antioxidant capacity (TAC) in antagonist mild and long agonist stimulations. MATERIALS AND METHODS: Forty patients received antagonist mild stimulation, starting on the 5th day of their cycle and forty patients received long agonist treatment. Seventy-five patients undergoing their first IVF cycle were included in the final analysis. Follicular fluid (FF) samples were analyzed for estradiol (E2), antimullerian hormone (AMH) and TAC. RESULTS: FF-Total antioxidant capacity (TAC) levels were higher in the long agonist group as opposed to the antagonist group [1.07 ± 0.04 mmol Trolox equivalent/L vs 1 ± 0.13 mmol Trolox equivalent/L] (Fig. 1). Pregnancy rates were not significantly different between the two treatments. The FF-TAC levels were not different among infertility etiologies (Fig. 3). FF-TAC levels did not have a direct correlation with pregnancy but a positive correlation with the total gonadotropin dose was observed. CONCLUSION: Patients with good ovarian reserves and under the age of 35 effectively responded to mild stimulation treatment. Using lower amounts of gonadotropin, yielded less FF-TAC levels in patients who underwent antagonist mild protocol. In patients under the age of 35, antagonist mild stimulation is a patient friendly and effective procedure when undergoing their first IVF cycle.

Lithium-induced hypothyroidism: oxidative stress and osmotic fragility status in rats.

The present study was conducted to explore the possible effects of different doses of lithium carbonate on thyroid functions, erythrocyte oxidant-antioxidant status, and osmotic fragility. Twenty-four Wistar-type male rats were equally divided into three groups: groups I and II received 0.1 and0.2 % lithium carbonate in their drinking water, respectively, for 30 days. The rats in group III served as controls, drinking tap water without added lithium. At the end of the experimental period, the erythrocyte osmotic fragility and the levels of triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were measured in blood samples. Compared to controls, there was a statistically significant increase of TSH but decreases of the T3 and T4 levels in group II. Both experimental groups showed a statistically significant increase of the maximum osmotic fragility limit. The minimum osmotic fragility values of the animals in group II were statistically higher than those of controls. The standard hemolytic increment curve of both experimental groups was shifted to the right when compared to the curve obtained from the controls. Also, relative to controls, the activities of MDA and SOD were significantly higher and the GSH level lower in group II, but not so in group I. The results of the present study show that treatment with lithium carbonate may result in thyroid function abnormalities, increased oxidative damage, and possible compromise of the erythrocyte membrane integrity resulting from increased osmotic fragility.

CCND1 and CDKN1B polymorphisms and risk of breast cancer.

BACKGROUND AND OBJECTIVES: Previous studies have shown alterations in the cell cycle regulatory proteins in breast carcinomas. However, the results of these studies remain controversial. Cyclin D1 (CCND1) and p27(KIP1) (CDKN1B) are two essential regulators of cell cycle progression. This study aimed to investigate the associations of CCND1 A870G and CDKN1B C79T polymorphisms with breast cancer risk. PATIENTS AND METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotype and allelic frequencies of polymorphisms. Seventy-eight breast cancer patients and 84 age-matched healthy controls were included in the study. RESULTS: Frequencies of CT genotype and T allele of CDKN1B were found to be higher in breast cancer patients than in controls (p=0.013, OR: 1.514 95% CI: 1.086-2.114.15; p=0.007, OR=1.496; 95% CI: 1.111-2.014, respectively). The frequency of AA genotype of CCND1 was decreased in hormone receptor- (estrogen and progesterone receptors) negative patients with breast cancer (p<0.049, OR=0.286; 95% CI: 0.071-1.142) CONCLUSIONS: Even though CDKN1B polymorphism appears to be an important predictive factor for breast cancer risk and CCND1 polymorphism may be a prognostic biomarker for breast cancer, further investigations with larger study groups are needed to fully elucidate the role of CCND1 and CDKN1B polymorphisms in the development and prognosis of breast cancer.

Alterations in lipid peroxidation and antioxidant status in different types of intracranial tumors within their relative peritumoral tissues.

OBJECTIVES: Elevated levels of lipid peroxidation and changes in the concentration of enzymatic and non-enzymatic antioxidant systems have been reported in various cancers, but there are very few reports available of lipid peroxidation due to oxidative stress in patients with intracranial neoplasms. The purpose of this study was to assess alterations in lipid peroxidation and antioxidant status in different types of tumors and to compare the results with their relative peritumoral tissues and compare the oxidative status in different grades of tumors. PATIENTS AND METHODS: We investigated the extent of oxidative stress and the levels of antioxidants in 16 astrocytomas and 38 other different types intracranial tumors comparing the results with their corresponding peritumoral tissues and comparing the levels in between low-grade and high-grade tumors. The extent of lipid peroxidation as evidenced by the formation of thiobarbituric acid-reacting substances (TBARS), as well as the status of the antioxidant systems such as superoxide dismutase (SOD), glutathione reductase (GR) and reduced glutathione (GSH) in tumor tissues and adjacent peritumoral tissues was estimated. The tumoral tissues were also compared as to their degrees of malignancy. RESULTS: According to our results lipid peroxidation in brain tumor tissues was enhanced compared to the corresponding adjacent peritumoral tissues. This was accompanied by a significant tumoral decrease in both enzymatic and non-enzymatic antioxidants. The low levels of antioxidants in tumor tissues, might be related to an increased use of antioxidant systems to scavenge lipid peroxides. Also a striking elevation in TBARS levels, and decrease in SOD activity and GSH levels were seen in high-grade tumors when compared with low grades. CONCLUSION: These findings emphasize a consistent difference in the level of antioxidants between the tumoral sample and its corresponding peritumoral tissue, independently of the tumoral type, and the most pivotal action would seem to minimise exposure to endogenous and exogenous sources of oxidative stress.

Investigation of tissue factor and other hemostatic profiles in experimental hypothyroidism.

The influence of thyroid failure on hemostasis has been studied and is still not well understood. These patients have high risk for cardiovascular diseases because of the lipid metabolism and procoagulant agents. But the influence of thyroid failure on hemostasis is controversial. Tissue factor (TF) has an important role in the thromboembolic state. Recent experiments have demonstrated that TF-dependent activation of the coagulation cascade plays an important role in the pathophysiology of intravascular thrombus formation. The purpose of the present study was to investigate the contributions of TF, factor VII:C (FVII:C), factor XII:C (FXII:C), and fibrinogen in experimental hypothyroidism. TF was obtained from the thyroid gland and lung tissue of 10 rats following experimental hypothyroidism induced for 30 d and compared with similar tissue from 10 control rats. Significantly increased TF activities were found in hypothyroid rats. By contrast, FVII:C level was significantly decreased when compared with the control group. In this respect it is interesting to note that a hypercoagulable state due to increased thromboplastic activity may occur. Based on those results, elevated tissue factor activities (TFa) of the patients with low thyroid dysfunction may have another risk factor for cardiovascular diseases.