Single and combined exposures to bisphenol A and benzophenone-3 during early mouse pregnancy have differential effects on fetal and placental development.

Endocrine disrupting chemicals (EDCs) possess the capability to interfere with the endocrine system by binding to hormone receptors, for example on immune cells. Specific effects have already been described for individual substances, but the impact of exposure to chemical mixtures during pregnancy on maternal immune regulation, placentation and fetal development is not known. In this study, we aimed to investigate the combined effects of two widespread EDCs, bisphenol A (BPA) and benzophenone-3 (BP-3), at allowed concentrations on crucial pregnancy processes such as implantation, placentation, uterine immune cell populations and fetal growth. From gestation day (gd) 0 to gd10, female mice were exposed to 4 µg/kg/d BPA, 50 mg/kg/d BP-3 or a BPA/BP-3 mixture. High frequency ultrasound and Doppler measurements were used to determine intrauterine fetal development and hemodynamic parameters. Furthermore, uterine spiral artery remodeling and placental mRNA expression were studied via histology and CHIP-RT-PCR, respectively. Effects of EDC exposure on multiple uterine immune cell populations were investigated using flow cytometry. We found that exposure to BP-3 caused intrauterine growth restriction in offspring at gd14, while BPA and BPA/BP-3 mixture caused varying effects. Moreover, placental morphology at gd12 and placental efficiency at gd14 were altered upon BP-3 exposure. Placental gene transcription was altered particularly in female offspring after in utero exposure to BP-3. Flow cytometry analyses revealed an increase in uterine T cells and NK cells in BPA and BPA/BP-3-treated dams at gd14. Doppler measurements revealed no effect on uterine hemodynamic parameters and spiral artery remodeling was not affected following EDC exposure. Our results provide evidence that exposure to BPA and BP-3 during early gestation affects fetal development in a sex-dependent manner, placental function and immune cell frequencies at the feto-maternal interface. These results call for inclusion of studies addressing pregnancy in the risk assessment of environmental chemicals.

Time course and attenuation of ischaemia-reperfusion induced oxidative injury by propofol in human renal transplantation.

Ischaemia-reperfusion injury resulting from interruption and restoration of blood flow might be related to free radical mediated oxidative stress and inflammation, and subsequently to post-surgery related complications. We studied the impact of renal transplantation on oxidative stress and inflammation by measuring F(2)-isoprostanes and prostaglandin F(2alpha), respectively, during transplantation and post-surgery. Additionally, due to earlier observations, two dissimilar anaesthetic agents (thiopentone and propofol) were compared to determine their antioxidative capacity rather than their anaesthetic properties. Blood samples were collected before, post-intubation, immediately, 30, 60,120, 240 min, and 12 and 24 h after reperfusion. Oxidative stress and inflammatory response were detected by measuring 8-iso-PGF(2alpha) (a major F(2)-isoprostane and a biomarker of oxidative stress) and 15-keto-dihydro-PGF(2alpha) (a major metabolite of PGF(2alpha) and a biomarker of COX-mediated inflammatory response), respectively. Reperfusion of the transplanted graft significantly increased plasma levels of 8-iso-PGF(2alpha). PGF(2alpha) metabolite levels, although elevated, did not reach statistical significance. In addition, significantly lower levels of 8-iso-PGF(2a) were observed in the propofol group compared to the thiopentone group. Together, these findings underline an augmented oxidative stress activity following an inflammatory response after human renal transplantation. Furthermore, propofol a well-known anaesthetic, counteracted oxidative stress by lowering the formation of a major F(2)-isoprostane.

Decreased wall shear stress in the common carotid artery of patients with peripheral arterial disease or abdominal aortic aneurysm: relation to blood rheology, vascular risk factors, and intima-media thickness.

BACKGROUND: Wall shear stress, a local risk factor of atherosclerosis, is decreased in the common carotid artery of patients with vascular risk factors. We evaluated wall shear stress in the common carotid artery of patients with symptomatic peripheral arterial occlusive disease (PAD) and abdominal aortic aneurysm (AAA). As blood viscosity is a determinant of wall shear stress, we further investigated the impact of rheologic variables on wall shear stress in relation to vascular risk factors and intima-media thickness. METHODS: High-resolution ultrasonography scans were used to study intima-media thickness, internal diameter, and blood velocity in the common carotid artery of 31 patients with PAD, 36 patients with AAA, and 37 controls. Furthermore, major hemorheologic variables and vascular risk factors were evaluated, and wall shear stress was calculated. RESULTS: Wall shear stress was lower in patients with PAD (median [IQR], dynes/cm(2): 14.4 [10 to 19]) and with AAA (12.1 [9 to 15]) than in healthy controls (20.6 [17 to 24]; P < .0001). Wall shear stress was inversely related to red cell aggregation (P = .01), fibrinogen (P = .003), leucocyte count (P = .001), plasma viscosity (P = .04), and intima-media thickness (P < .0001). Furthermore, wall shear stress was negatively associated with age, smoking, and triglycerides, but positively correlated with high-density lipoprotein cholesterol (all P < .001). When the influence of all these predictors were simultaneously taken into account in a multiple regression model, only age (P < .0001), smoking (P = .005), and triglycerides (P = .003) remained significantly associated with wall shear stress. CONCLUSIONS: This is the first report, to our knowledge, showing that wall shear stress of the common carotid artery is decreased in patients with symptomatic PAD and in patients with AAA. Rheologic variables are less important in predicting wall shear stress than age, triglycerides, and smoking.

Blood fluidity and outcome after femoropopliteal percutaneous transluminal angioplasty (PTA): role of plasma viscosity and low platelet count in predicting restenosis.

Rheological abnormalities are well known in patients with peripheral arterial occlusive disease (PAOD). We wanted to determine whether rheological variables are related to restenosis after femoropopliteal percutaneous transluminal angioplasty (PTA). In 114 patients (62 men; median age 70 years) undergoing femoropopliteal PTA for symptomatic peripheral arterial occlusive disease (PAOD) plasma viscosity, red cell aggregation, whole blood viscosity, hematocrit, fibrinogen, platelet count, leukocytes and C-reactive protein were determined the day after the procedure and at 1, 3, and 12 months. The primary endpoint was restenosis >50% documented by duplexsonography up to 12 months. Cox proportional hazards analysis was used to assess the risk of restenosis for postinterventional values of rheological variables. Forty-eight patients (42%) developed restenosis at 12 months. Patients with restenosis had higher baseline plasma viscosity (PV) (medians, 1.71 vs. 1.65 millipascal seconds [mPa.s]; p = 0.04) and lower platelet count (224 vs. 240 x 10(3)/microl; p = 0.03) than patients without restenosis. The hazard ratio (HR; 95% CI) of incident restenosis was 9.2 (1.12-76; p = 0.03) for PV and 0.99 (0.99-1.0; p = 0.07) for PLT. When examining jointly both high PV and low platelet count (PLT), patients with PV > 1.66 mPa.s and PLT < 233 x 10(3)/microl (i.e. variables split at their respective median) had an increased risk of restenosis (log-rank test p = 0.01). Multivariate Cox proportional hazard analysis showed that plasma viscosity (p = 0.02), low platelet count (p = 0.01), lesion length (p = 0.0037) and lack of hypertension (p = 0.01) were associated with restenosis at 12 months. No associations were found between restenosis and the other rheological and inflammatory variables studied. Our data suggest that increased PV and low PLT contribute to restenosis after femoropopliteal PTA.

C-reactive protein and red cell aggregation correlate with late venous function after acute deep venous thrombosis.

OBJECTIVE: Risk factors leading to development and subsequent progression of chronic venous insufficiency after acute deep venous thrombosis (DVT) are only partially identified. Inflammation and rheologic abnormalities might have a causative role. The purpose of this study was to investigate C-reactive protein (CRP), D -dimer, and blood rheologic parameters in patients after acute DVT in relation to clinical outcome. SUBJECTS AND METHODS: Patients with a history of acute proved DVT underwent clinical examination and duplex ultrasound scanning of the veins, and Venous Clinical Severity Score (VCSS) and Venous Segmental Disease Score (VSDS) were calculated. Further, CRP, D -dimer, and several rheologic parameters were determined and related to outcome as assessed with venous scores. RESULTS: Forty-three patients were examined 28 (median) months after the index event. Patients had higher CRP ( P < .001), D -dimer ( P < .001), red blood cell aggregation ( P < .01), fibrinogen concentration ( P < .01), and leukocyte count ( P < .05) than did healthy control subjects. CRP and red blood cell aggregation were positively correlated with VCSS ( r = 0.42 and P < .01, and r = 0.30 and P < 0.05, respectively). Multivariate regression analysis showed that the relation between CRP and VCSS was independent of other laboratory and rheologic parameters and of age, total thrombus load, duration of compression therapy after the index event, recurrence, recanalization, and presence of comorbid conditions ( P < .05). CONCLUSIONS: CRP is independently related to the severity of venous dysfunction in patients after acute DVT. Chronic inflammation as well as changes in blood rheologic parameters may be causally involved in the development of chronic venous insufficiency occurring in the medium-term and long-term course after acute DVT.