Correlation of single nucleotide polymorphisms in the promoter region of the ANXA5 (annexin A5) gene with recurrent miscarriages in women of Greek origin.

Background: Recent findings show that a number of single nucleotide polymorphisms (SNPs) within the promoter region of the annexin A5-gene (ANXA5) reduce the expression of the reporter gene and so they display a significant association with recurrent pregnancy loss (RPL).Objective: The objective of the present study aimed to address the contribution of ANXA5 M2 haplotype consisting of four minor alleles: (SNP1: (-)467G > A, SNP2: (-)448A > C, SNP3: (-)422T > C, and SNP4: (-)373G > A) in the occurrence of recurrent pregnancy losses in the Greek population, and the role of further two minor alleles: SNP5: (-)302 T > G and SNP6: (-)1C > T as independent risk factors for RPL.Methods: A 752-bp genomic region of ANXA5 promoter was amplified by PCR using specific primers. Genotypic analysis by Sanger sequencing was performed for these six SNPs (minor alleles) in the promoter region of ANXA5 gene, in 100 (100) Greek women with recurrent miscarriages (median =3) and 70 (70) fertile controls. Statistical analysis was done using the SAS 9.3 for Windows (SAS Institute Inc, NC, USA) and SPSS packages for Windows (C.DiMaggio 2013, SAS Institute 2014).Results: This case-control study revealed that there is no significantly increased risk of RPL among the M2/ANXA5 haplotype carriers in the Greek population, as there were no statistical differences between the patients with recurrent pregnancy losses and the fertile controls (11.5% in RPL cases versus 9.29% in controls, p-value: .6364). There was no difference in SNP5 and SNP6 minor carriership between the two groups. In particular, carriers of SNP5 and SNP6 had an increased risk for RPL state with odds ratio: 1.2472 and 1.3846 respectively, however without statistically significant importance.Conclusion: The M2/ANXA5 haplotype does not differ between RPL patients and controls in the Greek population. Also, it is the first time that SNP5 and SNP6 minor alleles were evaluated extensively in women of European origin with recurrent pregnancy losses (RPL), and they do not seem to be independent risk factors in the occurrence of RPL in the Greek population. Though, this has to be confirmed in further and larger clinical trials with women of European origin.

Genetic heterogeneity of platelet glycoproteins Ia and IIIa is associated with in vitro fertilisation implantation failure.

Thrombophilic genetic factors have been shown to play an important role in implantation outcome after in vitro fertilisation (IVF). In this pilot study we investigated the frequencies of glycoprotein Ia (GpIa)-C807T and GpIIIa-PlA1/PlA2 polymorphisms in 60 nulligravidae women with a history of unexplained IVF implantation failures and compared them with 60 healthy fertile women. We found statistically significant associations between the GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms and IVF implantation failure (odds ratio [OR] = 3.45, 95% confidence interval [CI]: 1.63-7.30, p = 0.001; and OR = 2.86, 95% CI: 1.27-6.45, p = 0.010, respectively) with the risk being higher for combined carriers of GpIa-807T and GpIIIa-PlA2 alleles (OR = 10.13, 95% CI: 2.85-35.99, p < 0.001), suggesting a synergistic effect of the two polymorphisms. The above associations were strongest for the youngest age group. Our results indicate that GpIa-807T and GpIIIa-PlA2 may be susceptibility alleles for IVF implantation failure.

Symptomatic Shigella sonnei urinary tract infection in pregnancy.

PURPOSE OF INVESTIGATION: This report describes a case of urinary tract infection (UTI) due to Shigella sonnei during pregnancy. METHODS: A 31-year-old pregnant woman was admitted complaining of left-flank tenderness, dysuria, and fever. RESULTS: Following examination, significant laboratory data were collected including increased leukocyte count (10,800/ul with 86% neutrophils) and C-reactive protein (9.6 mg/dl). Urinalysis revealed 30 to 50 leukocytes per high power field while from the quantitative urine culture Shigella sonnei was recovered after 24 h incubation at 37 degrees C. After a two-week course with 750 mg cefuroxime every 8 h, the patient experienced gradual resolution of all symptoms and urinary cultures were negative two weeks and one month, respectively, after completing the therapy. The gestational course was uneventful and the patient delivered a healthy baby girl at term. CONCLUSION: Shigella sonnei can be responsible for UTI during pregnancy even when no predisposing factors or an apparent source of infection can be identified.

MTHFR C677T polymorphism modifies the effect of HRT on metabolic parameters in postmenopausal women.

OBJECTIVE: To assess the interaction of the MTHFR C677T polymorphism with changes in lipid and glucose metabolism effected by oral hormone replacement therapy (HRT) in postmenopausal women. METHODS: In this open-label, prospective, interventional study, parameters of lipid and glucose metabolism, as well as homocysteine, were assessed in 97 postmenopausal women at baseline and 1 year after the initiation of HRT. Participants were stratified into three subgroups, according to the MTHFR C677T polymorphism (wild-type: CC genotype; heterozygous: CT genotype; homozygous for the mutant variable: TT genotype). RESULTS: The TT genotype was associated with an elevation of total and low density lipoprotein (LDL) cholesterol, while CT and CC genotypes were associated with a reduction of total cholesterol and LDL cholesterol after 1 year of HRT (p = 0.032 for total cholesterol and p = 0.002 for LDL cholesterol). Women with the TT genotype had higher glucose levels in contrast to women with the CC genotype who had lower glucose levels after 1 year of HRT (p = 0.011). Additionally, CC carriers under HRT had a significant elevation of apolipoprotein A1 levels (p = 0.018), contrarily to CT and TT genotypes. CONCLUSION: While HRT was associated with favorable changes in lipid and metabolic parameters in carriers of the CC genotype, this effect was not evident in carriers of the T allele. The MTHFR C677T polymorphism may modify the effect of HRT on lipid and metabolic parameters in postmenopausal women.

Effect of tibolone and raloxifene on serum markers of apoptosis in postmenopausal women.

OBJECTIVES: To investigate the effect of tibolone and raloxifene on the serum apoptotic markers soluble Fas (sFas), soluble Fas ligand (sFasL) and cytochrome-c (cyt-c) in postmenopausal women. METHODS: A total of 89 healthy postmenopausal women, attending the University Menopause Clinic, were randomly allocated to tibolone (n =30), raloxifene (n =29) or no treatment (n =30). Serum apoptotic markers sFas, sFasL and cyt-c were measured at baseline and at 6 months. RESULTS: Serum sFasL decreased significantly in women receiving tibolone (baseline: 53.8±28.3 pg/ml, 6 months: 40.45±19.2 pg/ml, p =0.001), whilst sFas levels did not significantly change in this group. Serum sFas or sFasL did not change either in the raloxifene group or in the control group. Serum cyt-c concentrations were under the detection limit of the assay in all women assessed. CONCLUSIONS: Tibolone use resulted in a significant decrease in serum sFasL, but not in serum sFas. Raloxifene had no effect on either sFas or sFasL. These results may indicate that tibolone use is associated with a decrease in receptor-mediated apoptosis.

The implication of second-trimester amniotic fluid TNF-alpha, cytochrome C and cell death nucleosomes in the prediction of preterm labor and/or premature rupture of membranes.

AIM: The multifactorial pathway leading to preterm labor possibly includes the implication of apoptosis. This study aimed to clarify the role of amniotic fluid apoptotic molecules (TNF-alpha, cytochrome C and cell death nucleosomes) at midtrimester as possible predictors of preterm labor (PTL) and/or premature rupture of membranes (PROM). METHOD: In this case-control study, comprising 360 women undergoing genetic amniocentesis and out of whom 38 delivered preterm and 18 out of the latter after PROM, the above apoptotic molecules were determined by ELISA. The 38 cases with PTL and 18 cases with PROM were matched for age with 38 and 18 respective controls delivering at term, and the levels of apoptotic molecules were compared. RESULTS: Cell death nucleosome levels were found to be significantly associated with preterm delivery. Specifically, for every unit increase in nucleosomes, women were on average 0.2% more likely to deliver preterm (OR: 1.002, CI: 1.0-1.003, p = 0.018). In contrast, such an association was not found concerning the other two apoptotic molecules (TNF-a and Cytochrome C). CONCLUSION: Second-trimester amniotic fluid cell death nucleosomes' levels are significantly associated with preterm delivery and could possibly serve as predicting markers.

Mid-trimester amniotic fluid interleukins (IL-1ß, IL-10 and IL-18) as possible predictors of preterm delivery.

AIM: Strong evidence implicates chronic intraamniotic inflammation in the etiology of preterm delivery. The purpose of this study was to determine whether amniotic fluid IL-1ß, IL-10 and IL-18 concentrations in women undergoing mid-trimester amniocentesis can identify those at risk for preterm labor or preterm rupture of membranes. PATIENTS AND METHODS: A case-control study was conducted to compare mid-trimester concentrations of amniotic fluid IL-1ß, IL-10 and IL-18 in women delivering at term or preterm. Out of 362 women included in the study, 38 presented with preterm labor. Thirty-eight women with term delivery, matched for chronological and gestational age served as controls. Women with abnormal fetal karyotypes or major anomalies were excluded. IL-1ß, IL-10 and IL-18 concentrations were determined by ELISA. Conditional logistic regression was applied in the statistical analysis. RESULTS: IL-1ß was found to be positively and significantly associated with preterm delivery. Specifically, for every unit increase in IL-1ß, women were on average 7.2 (OR: 7.2, CI: 1.94-26.77, p=0.003) times more likely to deliver preterm. IL-18 levels as well as gender were significantly associated with preterm delivery. Specifically, for every unit increase in IL-18, women were on average 1% less likely to have a preterm delivery (OR: 0.99, CI: 0.98-0.99, p=0.04). On the other hand, IL-10 was not significantly associated with preterm delivery. CONCLUSION: Mid-trimester IL-1ß concentrations are positively associated with preterm delivery. Therefore, IL-1ß, determined on the occasion of mid-trimester amniocentesis could possibly serve as a marker of preterm delivery. In contrast, IL-10 and IL-18 concentrations are not elevated in mid-trimester amniotic fluid and probably cannot serve this purpose.

BsmI vitamin D receptor's polymorphism and bone mineral density in men and premenopausal women on long-term antiepileptic therapy.

BACKGROUND: utilization of antiepileptic drugs (AEDs) has long been associated with bone deleterious effects. Furthermore, the BsmI restriction fragment polymorphism of the vitamin D receptor (VDR) has been associated with reduced bone mineral density (BMD), mostly in postmenopausal women. This study evaluates the association between bone metabolism of patients with epilepsy and the BsmI VDR's polymorphism in chronic users of AEDs. METHODS: this study evaluated 73 long-term users of antiepileptic drug monotherapy, in a cross-sectional design. Fasting blood samples were obtained to estimate the circulating serum levels of calcium, magnesium, phosphorus, parathormone, 25 hydroxyvitamin D as well as the VDR's genotype. Bone mineral density at the lumbar spine was measured with Dual Energy X-Ray Absorptiometry. RESULTS: bone mineral density was significantly associated with the genotype of VDR (mean BMD: Bb genotype 1.056 ± 0.126 g/cm(2) ; BB genotype 1.059 ± 0.113 g/cm(2) ; bb genotype 1.179 ± 0.120 g/cm(2) ; P < 0.05). Additionally, the presence of at least one B allele was significantly associated with lower bone mineral density (B allele present: BMD = 1.057 ± 0.12 g/cm(2) , B allele absent: BMD = 1.179 ± 0.119 g/cm(2) ; P < 0.01). Patients with at least one B allele had lower serum levels of 25 hydroxyvitamin D when compared with bb patients (22.61 ng/ml vs. 33.27 ng/ml, P < 0.05), whilst they tended to have higher levels of parathyroid hormone. DISCUSSION: vitamin D receptor polymorphism is associated with lower bone mass in patients with epilepsy. This effect might be mediated through the vitamin D-parathormone pathway.

The effect of hormone therapy and tibolone on serum CD40L and ADAM-8 in healthy post-menopausal women.

BACKGROUND/AIM: The role of neutrophils and platelets in atherothrombotic disease is well established. The aim of our study was to investigate the effect of HT and tibolone on the soluble markers of neutrophil and platelet activation, "a disentigrin and metalloproteinase domain" (ADAM-8) and CD40 ligand (CD40L) respectively, in healthy post-menopausal women. SUBJECTS AND METHODS: One hundred and six healthy post-menopausal women were randomly allocated to: estradiol plus drospirenone (E2/DSP), E2 hemihydrate 1 mg plus norethisterone acetate (E2/NETA) 0.5 mg, and tibolone 2.5 mg. Serum ADAM-8 and CD40L were measured at baseline and at 6 months. RESULTS: Baseline values of ADAM-8 and CD40L were similar between groups. No significant correlation was revealed between ADAM-8 or CD40L and parameters related to cardiovascular risk factors in each group. No significant changes were observed between baseline values and values at 6 months (E2/DSP group: ADAM-8: 267.4±71.3 pg/ml vs 270.7±42.8 pg/ml, p=0.86, CD40L: 6.43±3.13 vs 6.79±2.70 ng/ml, p=0.67), (E2/NETA group: ADAM-8: 308.3±64.3 vs 294.7±57.7 pg/ml, p=0.40, CD40L: 9.68±2.81 vs 8.59±5.13 ng/ml, p=0.51), (tibolone group: ADAM-8: 307.5±87.5 vs 289±48.1 pg/ml, p=0.48, CD40L: 9.46±4.30 vs 9.26±4.60 ng/ml, p=0.99). CONCLUSIONS: Our study has not revealed an association between estrogen plus progestin treatment or tibolone on serum ADAM-8 and CD40L levels in healthy post-menopausal women. Larger prospective studies are needed to further investigate the effect of low-dose HT or tibolone on serum markers of neutrophil and platelet activation.

Apolipoprotein E and paraoxonase 1 polymorphisms are associated with lower serum thyroid hormones in postmenopausal women.

OBJECTIVE: Autoimmune thyroiditis and overt or subclinical hypothyroidism have been associated with increased prevalence of cardiovascular disease (CVD). DESIGN: Cross-sectional investigation of the association between gene polymorphisms related to CVD with thyroid function and autoimmunity. PATIENTS: In total 84 healthy postmenopausal women aged 49-69 years. MEASUREMENTS: FT3, FT4, anti-TPO and anti-TG were assessed in the sera of participants. The following polymorphisms were assessed from peripheral lymphocyte DNA: Apolipoprotein E E2/E3/E4, paraoxonase 1 A/B, Glycoprotein IIIa leu33pro, MTHFR ala222val, ApoBarg3500gln, plasminogen activator inhibitor 1 4G/5G, cholesterol 7-alpha hydroxylase A204C and cholesterol ester transfer protein B1/B2. RESULTS: A statistically significant correlation was found between Apolipoprotein E and paraoxonase 1 polymorphisms and serum thyroid hormones: carriers of the E2 or E4 allele of the ApoE gene had lower levels of FT4 (P = 0.0005) than women with the E3/E3 genotype. Carriers of the B allele of paraoxonase 1 gene had lower levels of FT3 compared to women with the wild-type genotype (P = 0.047). A statistically significant positive association (P = 0.049) was also observed between anti-TG antibodies and the presence of the E2 allele of the Apolipoprotein E gene. CONCLUSIONS: Polymorphisms of apolipoprotein E and paraoxonase 1 are associated with different levels of thyroid hormone and anti-Tg antibody levels in the study population in this pilot study. The mechanism underlying this association remains to be elucidated.

Methylenetetrahydrofolate reductase C677T polymorphism is associated with central adiposity and increased androgenicity in healthy postmenopausal women.

OBJECTIVE: To assess the association of genetic polymorphisms related to cardiovascular disease (CVD) risk with anthropometric parameters and indices of androgenicity in healthy postmenopausal women. DESIGN: Cross-sectional study in a University Menopause Clinic. METHODS: The following polymorphisms were assessed in 84 healthy postmenopausal women: glycoprotein IIIa Leu33Pro, apolipoprotein E2/E3/E4, methylenetetrahydrofolate reductase (MTHFR) Ala222Val, apolipoprotein B Arg3500Gln, paraoxonase 1 Gln192Arg, plasminogen activator inhibitor 1 4G/5G, cholesterol-7 alpha-hydroxylase A-204C, and cholesterol ester transfer protein (TaqIB) B1/B2. Hormonal assays included FSH, LH, 17-beta-estradiol, testosterone, sex hormone-binding globulin (SHBG), DHEA sulfate, Delta-4-androstenedione (Delta4A), free androgen index (FAI), free estrogen index (FEI), and homocysteine (Hcy). The anthropometric components were body mass index (BMI) and waist-to-hip ratio (WHR). RESULTS: MTHFR Ala222Val polymorphism was positively associated with testosterone, FAI, and FEI (P=0.001, P=0.0004, and P=0.014 respectively) and negatively with SHBG (P=0.047). Furthermore, women bearing this polymorphism had higher BMI and WHR compared with women with the wild-type variant (P=0.027 and P=0.044 respectively). CONCLUSIONS: MTHFR Ala222Val polymorphism is associated with increased androgenicity and elevated BMI and WHR in healthy postmenopausal women. The significance of this association with respect to the CVD risk of postmenopausal women remains to be elucidated in future studies.

Cardiopulmonary arrest and resuscitation in Landrace/Large White swine: a research model.

Sudden cardiac death (SCD) is a field of continuous research. In order to answer various questions regarding SCD, several animal models have been developed. The aim of the present study is to describe our experimental model of inducing cardiac arrest in Landrace/Large White pigs, and then resuscitated according to the International Guidelines on resuscitation. Fifteen Landrace/Large White pigs were anaesthetized and intubated while spontaneously breathing. The left and right jugular veins, as well as the femoral and the carotid arteries, were surgically prepared. Induction of cardiac arrest was achieved by using an ordinary rechargeable lithium battery, through a pacemaker wire inserted into the right ventricle. The typical Advanced Life Support (ALS) protocol was followed, and in case of restoration of spontaneous circulation, the animals were further evaluated for 30 min. Seven animals were successfully resuscitated using this protocol, whereas eight failed resuscitation efforts. Successful resuscitation was contingent on the restoration of the levels of coronary perfusion pressure and PETCO(2) during chest compressions. Among the different ways of inducing cardiac arrest, the ordinary lithium battery is a simple, safe and valuable technique. Landrace/Large White pigs' baseline haemodynamics closely resemble human haemodynamics, making the breed a favourable model for resuscitation.

Chlamydia trachomatis infections in Greece: first prevalence study using nucleic acid amplification tests.

The present retrospective study was initiated to determine the prevalence of Chlamydia trachomatis and to assess the risk factors for infection in adult women and men presenting to general practitioners, gynecologists, dermatologists, and family-planning centers in Greece. The study was carried out in four different Greek hospital centers using highly sensitive nucleic acid amplification techniques. Altogether, 16,834 women and 1,035 men were enrolled from October 1998 to April 2004. Two types of specimens were collected from each patient: cervical swabs from women, urethral swabs from men, and first-catch urine from women and men. All specimens were examined with the Cobas Amplicor C. trachomatis polymerase chain reaction assay (Roche Molecular Systems, Branchburg, NJ, USA) or the LC x C. trachomatis ligase chain reaction assay (Abbott Laboratories, Abbott Park, IL, USA). Demographic and behavioral data were collected by clinicians using a standardized questionnaire. A total of 704 (3.9%) patients were infected with C. trachomatis. The prevalence among female patients was 3.5% and that among male patients 11.2%. Among infected patients, 88% were under 30 years of age, 71% reported more than one sexual partner, and 91% reported a new sexual partner within the last year. In conclusion, the prevalence of C. trachomatis infection in Greece is low. Young age and new and multiple sexual partners within the last year were factors consistently associated with an increased risk of chlamydial infection.

Effect of hormone replacement therapy, tibolone and raloxifene on serum lipids, apolipoprotein A1, apolipoprotein B and lipoprotein(a) in Greek postmenopausal women.

The aim of this study was to assess the effect of estrogen, two regimens of continuous combined hormone replacement therapy (HRT), tibolone and raloxffene on serum lipid, apolipoprotein A1 and B and lipoprotein(a) levels in Greek postmenopausal women. A total of 350 postmenopausal women were studied in a prospective open design. Women were assigned to one of the following regimens depending on the presence of risk factors for osteoporosis, dimacteric symptoms and an intact uterus: conjugated equine estrogen 0.625 mg (CEE, n = 34), continuous combined CEE 0.625 mg plus medroxyprogesterone acetate (MPA) 5 mg, (n = 80), continuous combined 17beta-estradiol 2 mg plus norethisterone acetate (NETA) 1 mg (n = 58), tibolone 2.5 mg (n = 83) and raloxifene HCl 60 mg (n = 50). Forty-five postmenopausal women with no indications for HRT served as controls. Total cholesterol (TC), low-density lipoprotein (LDL) cholestrol and high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and lipoprotein(a) (Lp(a)) levels were assessed in each subject at baseline, and at 6 and 12 months of therapy. All therapy regimens lowered TC levels compared to baseline (4.2-8.0% decrease). This effect was more prominent in the subgoup of women with high baseline TC levels (9.1-20.4% decrease). LDL cholesterol decreased significantly in CEE, CEE/MPA and raloxifene groups (-11.2%, -11.9% and -11.0%, respectively). Hypercholesterolemic women exhibited a steeper decrease in LDL cholesterol (10.6-27.8% in all therapy groups). TG levels increased significantly in the CEE and CEE/MPA groups (23.7% and 21.8%, respectively), while estradiol/NETA had no effect on TG levels. Tibolone decreased TG levels markedly, by 20.6%, while raloxifene had no TG-lowering effect. HDL cholesterol and ApoA1 were increased by CEE and CEE/MPA (HDL cholesterol, 7.4% and 11.8%, respectively; ApoA1, 17.8% and 7.9%, respectively) and decreased by tibolone (HDL cholesterol, -13.6%; and ApoA1, -9.9%). All therapy regimens except raloxifene lowered Lp(a) levels, with tibolone having the more pronounced effect (-13.2 to -29.0%). In conclusion, each therapy regimen had a diferent effect on lipid-lipoprotein levels, exerting favorable and unfavorable modifications. Hypercholesterolemic women seemed to benefit more from the cholesterol-lowering effect of estrogen replacement therapy/HRT. The choice for a particular regimen should be based on individual needs, indications and lipid-lipoprotein profile.

Hepatocyte function during experimental use of a bioartificial liver.

The aim of the present study was to compare the function of fresh versus cryopreserved hepatocytes in an experimental bioartificial liver system (BAL), especially designed to reproduce clinical parameters. Our BAL consists of a pump, a plasma reservoir, a membrane oxygenator, and a hollow fiber module loaded with 5 x 10(9) isolated porcine hepatocytes, either fresh (n = 5) or cryopreserved (n = 5). In the present setting, the system was isolated and perfused for 6 hours with recirculating plasma obtained from pigs with ischemic liver failure (toxic plasma). The following parameters were studied at 0 and 6 hours: oxygen consumption by the hepatocytes in the bioreactor, hepatocyte viability, as well as plasma concentrations of AST, LDH, ammonia, urea, and total bilirubin. MEGX concentrations were measured following injection of lidocaine into the system 30 minutes after initiation of plasma recirculation. Compared to cryopreserved cells, fresh hepatocytes showed higher viability at both time points studied (P <.05). Furthermore, during BAL sessions, ammonia levels were reduced while urea, AST, and LDH levels were increased with both preservation types (P <.05). Total bilirubin levels increased only during sessions with cryopreserved hepatocytes. After lidocaine administration, both fresh and cryopreserved hepatocytes were capable of producing MEGX; however, fresh-cell bioreactors produced significantly more MEGX at both 30 and 60 minutes after lidocaine administration. Oxygen consumption was significantly higher by fresh-cell bioreactors both before and after BAL use. In conclusion, hepatocytes in the BAL bioreactor showed preservation of important metabolic functions, when perfused with homologous toxic plasma. Fresh cells appeared to respond better than did cryopreserved ones.

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in plasma/serum and urine of women during term and threatened preterm labor: a clinical approach.

OBJECTIVE: To explore the concentrations of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in plasma, serum and urine of women during term and threatened preterm labor. METHODS: Plasma and urine proMMP-9 as well as serum and urine TIMP-1 were evaluated in 60 healthy pregnant women; 20 of them presented in term labor following an uncomplicated pregnancy, 20 of them presented with threatened preterm labor and intact membranes at 24-36 gestational weeks and 20 of them were at 24-40 gestational weeks with no evidence of uterine contractions or other pregnancy complications. Data were analyzed with non-parametric statistical tests and cut-off values were determined with receiver operator characteristic curves. RESULTS: ProMMP-9 values were significantly higher and TIMP-1 values were significantly lower in cases with uterine term or preterm contractions compared to non-labor status; and in cases with preterm contractions that progressed to true preterm labor compared to those in which contractions were arrested. CONCLUSIONS: Alterations in the concentrations of proMMP-9 and TIMP-1 can be detected in plasma or serum and urine of pregnant women experiencing term or preterm uterine contractions. The altered values of proMMP-9 and TIMP-1 could possibly identify the inevitable progress of preterm contractions to true preterm labor.

Effects of estrogen-progestin and raloxifene therapy on nitric oxide, prostacyclin and endothelin-1 synthesis.

This randomized double-blind study was conducted to investigate the effects of 17 beta-estradiol plus norethisterone acetate, and raloxifene, on nitric oxide (NO), prostacyclin (PGI2) and endothelin-1 (ET-1) serum levels in postmenopausal women. Treatment was initiated after a 28-50 day placebo period. Fourteen women were treated daily with 17 beta-estradiol 2 mg plus norethisterone acetate 1 mg (E2 + NETA), and 14 with raloxifene HCl 60 mg for a period of 6 months. Serum NO, PGI2 and ET-1 levels were estimated at baseline, after placebo, and at months 3 and 6. E2 + NETA decreased NO levels significantly, while raloxifene did not cause any appreciable change. Both regimens decreased PGI2 levels and ET-1 levels significantly. Finally, E2 + NETA and raloxifene increased the NO/ET-1 ratio by 61.4% and 81.1%, respectively. In conclusion, both regimens may exert a cardio-protective effect by decreasing ET-1 levels and increasing the NO/ET-1 ratio. In contrast, both regimens had a negative influence on PGI2 levels.

Immunohistochemical study of p185 HER2 and DF3 in primary breast cancer and correlation with CA-15-3 serum tumor marker.

Human epidermal growth factor receptor 2 (p185 HER2) oncoprotein immunohistochemical expression and DF3 antigen distribution were evaluated in 129 patients with primary breast cancer. p185 HER2 overexpession was positively correlated with the degree of differentiation, metastatic disease, progesterone receptors, and cytoplasmic distribution of DF3 antigen. p185 HER2 overexpression had prognostic significance for the disease-free interval.

Oxygen free radicals in abdominal aortic surgery. An experimental study.

BACKGROUND: In aortic reconstruction, intestinal and muscular ischaemia in the lower limbs occurs during cross-clamping of the aorta. After restoration of blood flow, reactive oxygen intermediates may lead to systemic injury to local or remote organs. In this study we investigated the usefulness of a shunt and vitamin E administration against the oxidant load generated in ischaemia-reperfusion phases. METHODS: In three groups of pigs (n=16) aortic reconstruction was simulated. In Group A (n=5) clamping of the infrarenal aorta was performed for 2 hours. In Group B (n=6), during aortic cross-clamping, a shunt was used to give flow to the inferior mesenteric and internal iliac arteries. In Group C (n=5) vitamin E was administered before aortic cross-clamping. In all groups we evaluated sigmoid histology after reperfusion, while the oxidant load was estimated by measuring superoxide dismutase (SOD) activity in blood samples from portal and jugular vein. RESULTS: Histology of the sigmoid revealed increased postischaemic injuries in Group A, while the protective effect of shunt and vitamin E was apparent in Group B and C, respectively. SOD activity was minimized in Group C. CONCLUSIONS: Vitamin E protected the sigmoid from postischaemic injury and is responsible for the decreased levels of SOD activity.

Fetoplacental leptin levels and their relation to birth weight and insulin in gestational diabetic pregnant women.

To investigate the fetoplacental leptin circulation in gestational diabetes, we compared cord leptin and insulin levels in 17 healthy pregnant women and 17 women with gestational-onset diabetes. Leptin levels in the umbilical arteries (mean+/-SD 1.80+/-0.76 ng/ml) were significantly (P<0.006) lower than those in umbilical veins (2.67+/-0.98 ng/ml) in normal pregnancies. Similarly, leptin levels in umbilical veins (mean+/-4.59+/-1.60 ng/ml) were significantly (P<0.001) higher than those in umbilical arteries (mean+/-SD 2.08+/-0.90 ng/ml) in gestational diabetes. However, leptin levels in umbilical veins were significantly higher (P<0.002) in gestational diabetes than those in controls. Additionally, in women with diabetes but not in controls, the birth weight and the cord leptin concentrations were positively related to cord insulin levels. We conclude that there is a hyperleptinaemia in the fetoplacental circulation in pregnant women with carbohydrate intolerance and in these cases insulin and leptin may have antagonist roles regarding fetal development.