Yvoni Koumantaki

Detection of interleukin-6, interleukin-8, and interleukin-11 in plasma from women with spontaneous abortion

OBJECTIVE To investigate the role of IL-6, IL-8, and IL-11 in the immune-regulatory mechanisms involved in the spontaneous abortion of the first trimester of pregnancy. STUDY DESIGN Plasma levels of IL-6, IL-8, and IL-11 were determined in 68 women who had a spontaneous abortion of unknown aetiology during the first trimester of pregnancy. They were compared with the corresponding levels of 73 age-matched pregnant women who had an uneventful pregnancy, and 52 age-matched non-pregnant women. All enrolled women presented without any severe disease, syndrome or recent infection. Cytokine levels were measured by a sensitive sandwich enzyme-linked immunoassay. RESULTS The women with spontaneous abortion had significantly decreased plasma levels of IL-6, IL-8 and IL-11 compared to those with normal pregnancies (P<0.05). The non-pregnant women had no detectable cytokine levels. CONCLUSIONS The reduced plasma levels of IL-6, IL-8 and IL-11 in women with spontaneous abortion may be related to the underlying aetiopathogenetic mechanisms, however, there is no sufficient evidence for their use as predictive markers of pregnancy outcome.

Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk

Colorectal cancer (CRC) is the third most common malignant tumor and the fourth leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in-depth analysis of inter-individual differences in fatty acid metabolizing genes as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. Three hundred and ninety two single-nucleotide polymorphisms were selected using pairwise tagging with an r(2) cutoff of 0.8 and a minor allele frequency of >5%. Conditional logistic regression models were used to estimate odds ratios and corresponding 95% confidence intervals. Haplotype analysis was performed using a generalized linear model framework. On the genotype level, hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), phospholipase A2 group VI (PLA2G6) and transient receptor potential vanilloid 3 were associated with higher risk for CRC, whereas prostaglandin E receptor 2 (PTGER2) was associated with lower CRC risk. A significant inverse association (P < 0.006) was found for PTGER2 GGG haplotype, whereas HPGD AGGAG and PLA2G3 CT haplotypes were significantly (P < 0.001 and P = 0.003, respectively) associated with higher risk of CRC. Based on these data, we present for the first time the association of HPGD variants with CRC risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and CRC risk.

Oral contraceptives, reproductive history and risk of colorectal cancer in the European prospective investigation into cancer and nutrition

Background:Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk.Methods:We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337 802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer.Results:After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83–1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74–0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk.Conclusion:Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk.

Erythropoietin in the treatment of iron deficiency anemia during pregnancy.

The aim of this study was to investigate the efficacy of recombinant human erythropoietin (rHuEPO) combined with parenteral iron, in the treatment of moderate and severe iron deficiency anemia during pregnancy. Twenty-six pregnant women, who had been ineffectively treated with iron supplementation alone for at least 8 weeks, were enrolled. They met the following criteria for inclusion in the study: hemoglobin (Hb) concentration <8.5 g/dl, evidence of iron deficiency anemia, and absence of other pregnancy complications, or severe systemic diseases. The treatment protocol comprised of a combination therapy with 150 IU/kg rHuEPO subcutaneously three times per week and 100 mg parenteral iron daily, for a total period of 4 weeks. Nineteen out of 26 women (73%) showed a quick response, with Hb reaching normal levels within the first 2 weeks of treatment. They displayed an average of 3.17 g/dl increase in Hb concentration during the total period of therapy, with 3.0 g/dl increase within the first 2 weeks. In 5 women (19.2%) there was no significant increase in Hb levels, while in 2 women (7.6%) a further decline in Hb concentration was observed, that necessitated a blood transfusion. In conclusion, rHuEPO combined with parenteral iron is an effective treatment for moderate and severe iron deficiency anemia during pregnancy, with minimal adverse or side effects. It may serve as an alternative to blood transfusion, or in cases of resistant anemia that are not effectively treated by iron supplementation alone. However, further studies are needed to investigate the poor response observed in about 25% of treated patients.

A prospective analysis of the association between macronutrient intake and renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition.

Previous case‐control studies have suggested that a high intake of animal foods and its associated nutrients are associated with an increased risk of renal cell carcinoma, although data from prospective studies are limited. We report here on the relationship between macronutrient intake and renal cell carcinoma incidence among 435,293 participants enrolled in the European Prospective Investigation into Cancer and Nutrition. Cox proportional hazard models were used to examine the association of dietary intake of fat, protein, carbohydrate, fiber and cholesterol and risk of renal cell carcinoma adjusted for age, sex, center, height, body mass index, physical activity, education, smoking, menopausal status, alcohol and energy intake. During an average 8.8 years of follow‐up, 507 renal cell carcinoma cases occurred. Risk of renal cell carcinoma was not associated with macronutrient intake, including nutrients derived from animal sources. Our results indicate that macronutrient intake is not associated with risk of renal cell carcinoma in this cohort of European men and women.

A randomized comparison of danazol and leuprolide acetate suppression of serum-soluble CD23 levels in endometriosis.

Objective To determine the effects of treatment with danazol and leuprolide acetate depot on serum-soluble CD23 concentrations in women with endometriosis. Methods This randomized trial involved 20 women 18–42 years old with regular menses and known pelvic endometriosis who were recruited from a university hospital between 1993 and 1998. Ten women took 200 mg of danazol three times daily for 6 months, and the remaining ten were given 3.75 mg of leuprolide acetate depot every 28 days for 6 months. Blood-soluble CD23 levels were measured before treatment, during the last 15 days of the 6-month treatment course, and 3 months after treatment. Only one blood sample was taken from ten women without endometriosis, between the 5th and 7th days of their menstrual cycles. For statistical analysis, we used independent and paired t tests with the Pearson correlation coefficient. Results Soluble CD23 levels were significantly higher in women with endometriosis before treatment than in ten normal controls. Levels decreased significantly during treatment with either danazol or leuprolide acetate. Three months after treatment, soluble CD23 values remained lower than before treatment. There was no correlation between soluble CD23 concentrations and severity of endometriosis. Conclusion Our findings suggest that endometriosis increases soluble CD23 levels, which can be suppressed with either danazol or leuprolide acetate injection.

Plasma Carnitine Levels of Pregnant Adolescents in Labor

STUDY OBJECTIVE To determine the concentration of plasma carnitine (total, free, and acylcarnitine) during the delivery of uncomplicated pregnancies of adolescent women. To investigate the relationship between maternal and neonatal levels of carnitine and to compare these carnitine levels between pregnant and nonpregnant adolescents. DESIGN Samples of maternal and umbilical blood were taken at the time of delivery and examined for the determination of the carnitine-total, free, and acylcarnitine-concentration by the use of an enzymatic-radioisotope method. Twenty-two cases of uncomplicated adolescent pregnancies with a normal labor and without perinatal complications were examined. The plasma level of carnitine was also examined in 17 healthy nonpregnant adolescent women, which constituted the control group. RESULTS The concentrations of plasma carnitine in adolescent pregnancies at the time of delivery were calculated at 19.6 +/- 2.15 microMol/L (total), 12.62 +/- 1.31 microMol/L (free), and 6.98 +/- 1.55 microMol/L (acylcarnitine). The corresponding mean values in umbilical plasma were 30.31 +/- 2.06 microMol/L, 22.39 +/- 1.64 microMol/L, and 7.92 +/-.96 mucroMol/L. There is a statistically significant difference between the mean values in maternal and umbilical plasma (P <.0001 for total and free carnitine and P <.012 for acylcarnitine). The correlations between adolescent pregnant women and their infants as regards total, free, and acylcarnitine were 0.137, 0.018, and 0.33, respectively. Neither of these parameters was statistically significant. The corresponding mean values of carnitine in nonpregnant adolescent women were statistically significantly higher than in adolescent pregnant women (total carnitine: 41.61 +/- 3.09 microMol/L, free: 31.39 +/- 2.81 microMol/L, acylcarnitine: 10.22 +/- 1.88 microMol/L, P <.0001). CONCLUSIONS The concentration of plasma carnitine at the end of adolescent pregnancy is low compared to the levels of umbilical carnitine at birth and that found in nonpregnant adolescent women. It may not have an obvious impact on the utilization of fatty acids in an uncomplicated full-term pregnancy; however, it suggests the potential risk for neonatal fatty-acid oxidation in a preterm or complicated pregnancy.