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.

Views of cancer patients regarding cardiopulmonary resuscitation in Greece.

Cardiopulmonary resuscitation (CPR) in patients with cancer is an ethical issue of worldwide interest. A questionnaire-based study was carried out in a Greek oncology hospital aiming to explore the attitude of Greek cancer patients towards CPR. Overall, 200 patients (94 male, 106 female) of a mean age of 62.8 years took part in the study. Only 42 (21%) patients indicated that they knew what CPR really involves and only 20 (10%) patients thought that CPR has serious side effects, while the mean estimated in-hospital CPR survival rate to hospital discharge was 56.6% (minimum = 2%, maximum = 99%, standard deviation [SD] = 25.16) and 42.1% (minimum = 0%, maximum = 90%, SD = 24.56%) in case of unselected and cancer patients respectively. Despite their poor knowledge, 177 (88.5%) patients were willing to undergo CPR in case of an in-hospital arrest, 127 (63.5%) thought that they had the right to choose their CPR status and 141 (70.5%) believed that they should be asked about it when they enter the hospital. Most patients (36%) wanted their CPR status to be decided by themselves, their family and their doctor jointly. These findings indicate that specific measures should be applied to clinical practice in order to best manage this ethical issue, and consequently, improve cancer care.

The presence of CD40, CD40L and ADAM8 among endometriotic patients.

Clinical and molecular research data are still insufficient to determine the onset, etiology and progression of endometriosis. Recently, a number of studies have been investigating the role of the inflammatory-immune factor. The role of inflammation in tissue infiltration and staging of endometriosis is limited. The aim of this study is to investigate the presence of CD40, CD40L and ADAM8 among endometriotic patients. These three markers of inflammation were measured in the serum of each of 76 women participating in the study. Twenty-nine (29) women, of mean age 36.9, (±9.2 SD) years free of endometriosis served as the control group. Of the endometriotic women 15 had a stage I-II and 32 stage III-IV disease. We undertook the present investigation expecting that an increased expression of CD40, CD40L and ADAM8 would testify to the inflammatory-autoimmune character of endometriosis. No difference in the levels of CD40, ADAM 8, CD40L was detected between the two groups. The stage of endometriosis did not affect CD40, ADAM 8, CD40L serum concentrations. A difficulty in our study is the lack of data with which to compare our results. Further investigation is needed to elucidate the role of these inflammatory markers in endometriosis.

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.

Long-term effect of low molecular weight heparin on serum lipids in hypertriglyceridemic chronic hemodialysis patients.

Although low-molecular-weight heparin (LMWH) has been reported to lower serum triglycerides and raise HDL in patients previously receiving classic heparin for hemodialysis by sparing lipoprotein lipase activation, this is not universally accepted. To evaluate this effect we studied 14 hypertriglyceridemic patients on hemodialysis for a median of 61 months (range 6-168 months); six were males and eight females, with a median age of 54 years (range 30-78). Eight patients were on bicarbonate and six on acetate HD. Eight were receiving EPO. All had been given conventional heparin, 102 +/- 5.8 IU/kg, at least for the last six months (control period) before switching to LMWH. Mean LMWH dose was 77 +/- 3.1 IU/kg. Fasting levels of total cholesterol (TC), triglycerides (TG) and HDL were measured monthly during the control period and every trimester for the next 36 months. Serum lipoproteins were measured at months 0 and 36 of the trial. TC, Lp alpha and beta showed no significant change. Serum TG and Lp pre-beta dropped significantly, to almost normal levels. EPO treatment, serum iPTH levels or dialysate buffer did not seem to influence this effect. HDL rose significantly higher in women than in men. It is concluded that LMWH substantially lowered the abnormally high serum TG and Lp pre-beta to almost normal and raised serum HDL in chronic hemodialysis patients.

Changes of arterio-venous differences in pH and pCO2 by hemodialysis.

Normally the differences in arterial-venous pH (A-VpH) and veno-arterial pCO2 (V-ApCO2) are small and constant. This study deals with A-VpH and V-ApCO2 and their effect on arterial-venous saturation hemoglobin percentage (A-VSHb%) in uremic patients under hemodialysis (HD). In 17 uremic patients under HD with acetate, blood samples were collected anaerobically in heparinized syringes from artery (fistula) and vein (forearm without fistula) pre- and post-HD. In these samples pH, pCO2 and SHb% were determined and A-VpH, V-ApCO2 and A-VSHb% were estimated. Comparison between the values pre- and post-HD of A-VpH, V-ApCO2 and A-VSHb% shows that these three values were decreased significantly post-HD (p < 0.001). The correlation of all values (pre- and post-HD) of A-VpH and V-ApCO2 with that of A-VSHb% was significant and positive (r = 0.514 p < 0.01, r = 0.505 p < 0.01, respectively).

Serum ferroxidase I and II in uremic patients under conservative treatment and maintenance hemodialysis.

Serum ferroxidase I (ceruloplasmin) and ferroxidase II activities were studied in 49 uremic patients under conservative treatment, in 79 patients undergoing hemodialysis and in 56 healthy subjects, as controls. Ferroxidase I was significantly higher in both groups of patients. Ferroxidase II was significantly elevated only in patients undergoing chronic hemodialysis. The cause of this difference is not clear, but seems to be of considerable interest.