Influence of VKORC1 gene polymorphisms on the effect of oral vitamin K supplementation in over-anticoagulated patients

Significant inter-individual variability on the effect of vitamin K to reverse overanticoagulation has been identified. Genetic polymorphisms of the vitamin K epoxide reductase complex subunit 1 (VKORC1) gene might explain in part this variability. The objective of this study was to evaluate the influence of VKORC1 ?1639G>A and 3730G>A polymorphisms on the effect of oral vitamin K supplementation in overanticoagulated patients. We performed an interventional trial of oral vitamin K supplementation in over-anticoagulated outpatients (international normalized ratio [INR] ≥ 4). Subjects received vitamin K (2.5–5.0 mg) according to baseline INR and were genotyped by real time polymerase chain reaction (PCR). INR values were determined at 3, 6, 24 and 72 h after supplementation. We evaluated 33 outpatients, 61 % were males, with a mean age of 62 ± 12 years old. There was a significant decrease in INR values over time for both polymorphisms after oral vitamin K. At 3 h after supplementation, patients carrying the G allele for the ?1639G>A polymorphism had a greater decrease in INR values compared to AA patients (p < 0.05 for difference among groups; p < 0.001 for time variation; p = 0.001 for time × group interaction), with differences of ?1.01 for GG versus AA (p = 0.003) and ?0.84 for GA versus AA (p = 0.024). Mean INR value at 24 h was 1.9 ± 0.6 and at 72 h was 2.1 ± 0.7, with no differences among genotypes. No significant interaction was identified between the 3730G>A polymorphism and vitamin K supplementation. Our study indicated that the VKORC1 ?1639G>A polymorphism plays a role in the response to acute vitamin K supplementation in over-anticoagulated patients, with faster decrease of INR value in patients carrying the G allele.     

Factors Associated with Prenatal Care and Seeking Assistance in Public Hospitals in Vitória,Espírito Santo,Brazil

Adequate prenatal care provides an opportunity for counseling and reducing the complications associated with pregnancy and delivery. Our objective was to describe the demographic, behavioral, and clinical profile of the pregnant women hospitalized at public maternity hospitals and to identify factors associated with six or more prenatal consultations in Vitória, Brazil. A cross-sectional study of 1,380 women was conducted in public maternity hospitals in Vitória, Brazil. Sixty-seven percent of participants had ≥6 prenatal consultations. Reasons for hospitalization were vaginal delivery (55.7%), cesarean section (32.9%), clinical treatment (7.7%), and abortion/miscarriage (3.7%). Having ≥9 years of schooling (odds ratio, OR = 1.8; 95% confidence interval, CI: 1.1–3.1), being married (OR = 1.9; 95% CI: 1.2–2.9) and delivering at term (OR = 3.6; 95% CI: 1.6–8.2) were significantly independently associated with having ≥6 prenatal consultations. Although higher education, being married, and delivering at term were associated with ≥6 prenatal consultations in this population, the high rate of Cesarean sections demonstrates the need for ongoing educative strategies among health professionals.     

Longer Times of Receipt of Adjuvant Endocrine Therapy Correspond to Improved Functional Capacity and Lower Adiposity in Women Receiving Adjuvant Therapy

Purpose

To study the use of functional capacity (FC) level and duration of aromatase inhibitor (AI) therapy with adiposity parameters in women with breast cancer.

Dendritic cells regulate angiogenesis associated with liver fibrogenesis

During liver fibrogenesis the immune response and angiogenesis process are fine-tuned resulting in activation of hepatic stellate cells that produce an excess of extracellular matrix proteins. Dendritic cells (DC) play a central role modulating the liver immunity and have recently been implicated to favour fibrosis regression; although their ability to influence the development of fibrogenesis is unknown. Therefore, we explored whether the depletion of DC during early stages of liver injury has an impact in the development of fibrogenesis. Using the CD11c.DTR transgenic mice, DC were depleted in two experimental models of fibrosis in vivo. The effect of anti-angiogenic therapy was tested during early stages of liver fibrogenesis. DC depletion accelerates the development of fibrosis and as a consequence, the angiogenesis process is boosted. We observed up-regulation of pro-angiogenic factors together with an enhanced vascular endothelial growth factor (VEGF) bioavailability, mainly evidenced by the decrease of anti-angiogenic VEGF receptor 1 (also known as sFlt-1) levels. Interestingly, fibrogenesis process enhanced the expression of Flt-1 on hepatic DC and administration of sFlt-1 was sufficient to abrogate the acceleration of fibrogenesis upon DC depletion. Thus, DC emerge as novel players during the development of liver fibrosis regulating the angiogenesis process and thereby influencing fibrogenesis.