Higher preprocedural fibrinogen levels are associated with aneurysm sac regression after EVAR.

Background: The aim of our study was to determine the diameter of the aneurysm sac 24 months after endovascular abdominal aortic aneurysm repair (EVAR); to identify factors associated with sac regression, and to determine the impact of sac regression on all-cause mortality during long-term follow-up. Patients and methods: We conducted a retrospective review of prospectively collected data from patients treated with EVAR between January, 2010 and July, 2016. Sac regression was defined as at least 5 mm decrease in aneurysm diameter in relation to the preprocedural diameter seen on computed tomography angiography. Sociodemographic information, comorbidities, treatment, laboratory parameters, selected anatomical and genetic factors were all analysed to determine their impact on sac regression. Results: During the study period, 124 patients with mean age of 71.2 ± 7.2 years met the inclusion criteria. Sac regression was found in 45.2% of patients. Higher preprocedural fibrinogen was found in patients with sac regression in comparison with patients with stable sac or sac expansion (3.84 g/l vs 3.47 g/l; p = 0.028). In multivariate analysis after adjustment for age, hypertension, sex, smoking, dyslipidaemia, volume and percentage of intraluminal thrombus higher fibrinogen was associated with an increased probability of sac regression (OR 2.47; 95% CI 1.29-4.72; p = 0.006). Persistent type II endoleak was associated with significantly lower probability of sac regression in univariate and multivariate analysis after adjustment for age, hypertension, sex, smoking and dyslipidaemia (OR 0.26; 95% CI 0.10-0.66; p = 0.004). Higher age was a significant predictor of sac regression in multivariate analysis after adjustment for hypertension, sex, smoking and dyslipidaemia (OR 1.07; 95% CI 1.02-1.14; p = 0.012). No difference was found between patient subgroups with and without sac regression in all-cause mortality during follow-up. Conclusions: Higher preprocedural fibrinogen, absence of persistent type II endoleak and higher age were predictive factors of aneurysm sac regression post-EVAR.

Relationship Between the Apolipoprotein E Genotype and LDL Particle Size in Patients With Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is associated with dyslipidemia and increased cardiovascular risk. We assessed the effects of apolipoprotein E ( APOE) genotype on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle size and lipid subclasses (separated by gradient gel electrophoresis) in patients with OSA. Stable patients (n = 181) prospectively recruited underwent full polysomnography. Both LDL particle size and LDL I proportion were reduced from ∊3∊3 homozygotes to ∊2 carriers and to ∊4 carriers (analysis of variance: P = .024; P = .040, respectively); carriers of the ∊4 allele of the APOE genotype had significantly lower LDL particle size and LDL I proportion compared to ∊3∊3 homozygotes ( P < .05 for both comparisons). Insulin resistance increased from patients with no OSA to those with mild-moderate and to those with severe OSA ( P < .001). In multivariate analysis, LDL size was independently predicted by APOE genotype, male gender, and the presence of metabolic syndrome (MetS; P = .001, P = .020, P = .027, respectively). The HDL particle size was not affected by APOE genotype. Our data demonstrate that both the ∊4 APOE genotype and MetS are independently related to smaller LDL size in patients with OSA.

Gene Polymorphism of the Adenosine A2a Receptor in Patients with Vasovagal Syncope.

BACKGROUND: Adenosine may play a role in the pathogenesis of vasovagal syncope (VVS). The aim of the study was to evaluate the adenosine A(2A) receptor gene 1083 T > C polymorphism in patients with syncope and its possible association with results of head-up tilt test (HUT). METHODS: Three hundred and forty-seven consecutive patients (mean age 47.3 ± 18.5 years, 132 men, 215 women) with one or more syncopal episodes underwent HUT as part of standardized diagnostic evaluation. HUT was positive in 207 patients (75 males, mean age 44.7 ± 18.6 years) and negative in 140 patients (58 males, mean age 48.17 ± 18.8 years). One thousand and eighty-three T > C single nucleotide polymorphism in the adenosine A(2A) receptor gene (rs5751876) was evaluated in 347 patients with syncope and in 85 subjects without history of syncope (54 men, mean age 41.7 ± 16.3). RESULTS: Adenosine A(2A) receptor 1083 T > C polymorphism was not associated with the positivity of HUT. Blood pressure and heart rate response to tilting was similar in all genotypes. Low frequency (LF) power was significantly lower in CC genotype compared to CT genotype in early phase of tilt (log LF 2.69 ± 0.61 vs 3.20 ± 0.60; P = 0.01) and at the time of syncope (log LF 2.60 ± 0.63 vs 2.77 ± 0.48; P = 0.04). CONCLUSIONS: Adenosine A(2A) receptor 1083 T > C polymorphism is not associated with the positivity of HUT and its proposed role in predisposition to VVS was not confirmed. CC genotype may be associated with lower sympathetic activity during HUT.

Effects of apolipoprotein E genotype on serum lipids in obstructive sleep apnoea.

There is increasing evidence that intermittent hypoxia resulting from obstructive sleep apnoea (OSA) is independently associated with dyslipidaemia. Currently, no data exist on potential links between OSA-related dyslipidaemia and susceptibility genes for dyslipidaemia in such patients. Our aim was to study the effects of the apolipoprotein E (APOE) genotype and sleep apnoea severity on atherogenic dyslipidaemia in patients with OSA. 519 clinically stable subjects prospectively recruited at a tertiary referral teaching hospital underwent full polysomnography. APOE gene polymorphisms were assessed using real-time PCR. In all APOE genotype groups, serum triglycerides increased while high-density lipoprotein (HDL) cholesterol was reduced with increasing severity of OSA in each APOE genotype group, whereas the deleterious effects of OSA on serum apolipoprotein (Apo)B levels were observed in ε2 carriers and the ε3/ε3 genotype only. Nevertheless, the ε4 allele carriers had ApoB levels within the risk range, irrespective of nocturnal hypoxia. In addition, among patients with the high-risk ε4 genotype, those with the most severe nocturnal hypoxia had significantly higher triglyceride and lower HDL cholesterol levels compared with nonhypoxic ε4 subjects. APOE genotype and the oxygen desaturation index were both independent predictors of serum triglyceride levels (p=0.009 and p<0.001, respectively; R(2)=0.148) and ApoB levels (p=0.001 and p=0.003, respectively; R(2)=0.104). Our findings suggest that OSA has adverse effects on several lipid parameters over and above the effects carried by APOE genotype. Further st1udies are needed to analyse the effects of high-risk genotypes on metabolic and cardiovascular outcomes in patients with OSA.

Effects of docetaxel, doxorubicin and cyclophosphamide on human breast cancer cell line MCF-7.

BACKGROUND: Cell viability assays are important tools in oncological research. The purpose of this study was to evaluate the effect of docetaxel, doxorubicin and cyclophosphamide on the metabolic activity of MCF-7 breast cancer cell line. MATERIALS AND METHODS: Antiproliferative effect of cytostatics on MCF-7 cells was measured using the standard colorimetric test. The MCF-7 cell line was exposed to cytostatics for 24 hours. The metabolic activity was evaluated over the 24 hours. RESULTS: According to the statistical analysis, the change in the growth rate was significant (p<0.05) for the 120 nM docetaxel and above the 200 nM doxorubicin treatment in comparison with sensitive MCF-7 cells. When considering drugs in combination (60 nM docetaxel with 200 nM doxorubicin and 60 nM docetaxel with 500 nM doxorubicin) after the addition of 600 nM cyclophosphamide, we found a statistically significant decrease of metabolic activity of the MCF-7 cell line (p<0.05). CONCLUSION: Cyclophosphamide at 600 nM seems to enhance the influence of docetaxel when combined with doxorubicin.

The role of the -427T/C apolipoprotein E promoter polymorphism in the pathogenesis of Alzheimer's disease, vascular dementia and mixed dementia.

In this work, we explored the existence of genetic variant within the apolipoprotein E gene transcriptional regulatory region. Upon a population study, three polymorphic sites (-491, -427 and -219) and two mutations were found. We investigated newly reported -427T/C promoter polymorphism in association with sporadic Alzheimer's disease (AD), vascular (VD) and mixed dementia (MD) along with APOE genotype and gender. Observed polymorphisms were investigated in 267 subjects, 122 of them formed a control group, the group of patients consisted of 145 subjects. Sixty patients were diagnosed with AD, 41 patients were diagnosed with VD and 35 patients left were diagnosed with MD in Slovak Caucasians (Central Europe). Gene-gene interaction analysis showed increase of the risk to develop AD in subjects carrying both the at least one C allele and the APOE E4 allele (OR = 17.93, 95%CI = 3.50-171.54).

Beta2-adrenergic receptor haplotype and bronchodilator response to salbutamol in patients with acute exacerbations of COPD.

BACKGROUND: The role of the beta2-adrenergic receptor (ADRB2) genotype in patients with chronic obstructive pulmonary disease (COPD) is unclear. In patients with acute exacerbations of COPD (AECOPD), we assessed the role of ADRB2 haplotypes in morning lung function and in the bronchodilator response to salbutamol. MATERIAL/METHODS: In 107 patients with AECOPD, polymorphisms in the amino acid position 16 (Arg16/Gly16) and 27 (Gln27/Glu27) of the ADRB2 gene were assessed by allele-specific polymerase chain reaction, identifying 31 subjects with the Gly16/Glu27-negative and 76 with the Gly16/Glu27-positive ADRB2 haplotype. Pulmonary function and bronchodilator response to salbutamol were assessed using bodyplethysmography. RESULTS: Forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) were significantly higher in the Gly16/Glu27-negative compared to the Gly16/Glu27-positive haplotype group at baseline (49.7+/-2.9% vs 42.4+/-1.8% predicted, P=0.037; 44.0+/-2.2% vs 36.4+/-1.6% predicted, P=0.008, respectively). FEV1, PEF, and forced vital capacity (FVC) increased from baseline to after salbutamol treatment in both the Gly16/Glu27-negative and the Gly16/Glu27-positive ADRB2 haplotype groups (P<0.001 for all comparisons). Values for FEV1 and PEF after administration of the bronchodilator were significantly higher in the Gly16/Glu27-negative haplotype group compared with the Gly16/Glu27-positive haplotype group (P=0.030 and P=0.034, respectively). No differences were observed in DeltaFEV1, DeltaPEF, or DeltaFVC after bronchodilation between the 2 ADRB2 haplotype groups (12.2+/-1.8% vs 14.5+/-1.5% predicted, P=0.393; 12.2+/-3.3% vs 20.8+/-3.2% predicted, P=0.117; 9.1+/-2.3% vs 10.4+/-1.9% predicted, P=0.707, respectively). CONCLUSIONS: The present findings suggest that the ADBR2 gene haplotypes may affect the severity of obstructive ventilatory impairment but not the immediate response to salbutamol during AECOPD.

Glutathione S-transferase and microsomal epoxide hydrolase gene polymorphisms and risk of chronic obstructive pulmonary disease in Slovak population.

AIM: To determine the risk of chronic obstructive pulmonary disease (COPD) associated with polymorphisms in the glutathione S-transferase (GST) M1, GST T1, and microsomal epoxide hydrolase (EPHX1) genes in a cohort of Slovak population. METHODS: Two hundred and seventeen patients with the diagnosis of COPD and 160 control subjects were enrolled in the study. Blood samples were collected from all subjects and the DNA from peripheral blood lymphocytes was used for subsequent genotyping assays, using polymerase chain reaction and restriction fragment-length polymorphism methods. RESULTS: In an unadjusted model, an increased risk for COPD was observed in subjects with EPHX1 His113-His113 genotype (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.20-4.69; P=0.008), compared with the carriers of the Tyr113 allele. However, after the adjustments for age, sex, and smoking status, the risk was not significant (adjusted OR, 1.79; 95% CI, 0.91-3.53; P=0.093). In a combined analysis of gene polymorphisms, the genotype combination EPHX1 His113-His113/GSTM1 null significantly increased the risk of COPD in both, unadjusted (OR, 5.08; 95% CI, 1.70-20.43; P=0.001) and adjusted model (OR, 4.87; 95% CI, 1.57-15.13; P=0.006). CONCLUSION: Although none of the tested gene polymorphisms was significantly related to an increased risk of COPD alone, our results suggest that the homozygous exon 3 mutant variant of EPHX1 gene in the combination with GSTM1 null genotype is a significant predictor of increased susceptibility to COPD in the Slovak population. The findings of the present study emphasize the importance of detoxifying and antioxidant pathways in the pathogenesis of COPD.