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.     

Involvement of PKCα–MAPK/ERK-phospholipase A2 pathway in the Escherichia coli invasion of brain microvascular endothelial cells

Escherichia coli K1 is the most common Gram-negative organism that causes neonatal meningitis following penetration of the blood–brain barrier. In the present study we demonstrated the involvement of cytosolic (cPLA₂) and calcium-independent phospholipase A₂ (iPLA₂) and the contribution of cyclooxygenase-2 products in E. coli invasion of microvascular endothelial cells. The traversal of bacteria did not determine trans-endothelial electrical resistance (TEER) and ZO-1 expression changes and was reduced by PLA₂s siRNA. cPLA₂ and iPLA₂ enzyme activities and cPLA₂ phosphorylation were stimulated after E. coli incubation and were attenuated by PLA₂, PI3-K, ERK 1/2 inhibitors. Our results demonstrate the role of PKCα/ERK/MAPK signaling pathways in governing the E. coli penetration into the brain.     

Acute effects of aerobic exercise on mood and hunger feelings in male obese adolescents: a crossover study

ABSTRACT: BACKGROUND: The aim of this study was to determine the acute effects of exercise intensity on anxiety, mood states and hunger in obese adolescents. METHODS: Subjects were eight male obese adolescents (age 15.44 +/- 2.06y; BMI 33.06 +/- 4.78 kg/m2). Each subject underwent three experimental trials: 1) Control, seated for 30 min; 2) Low intensity exercise (LIE) - exercise at 10% below ventilatory threshold (VT); 3) High intensity exercise (HIE) - exercise at 10% above VT. Anxiety (STAI Trait/State), mood (POMS) and hunger (VAS) were assessed before and immediately after the experimental sessions. Comparisons between trials and times were assessed using Kruskal-Wallis and Wilcoxon tests, respectively. Associations between variables were described using a Spearman test. RESULTS: The largest increase in hunger was observed after LEI (914.22%). Both exercise sessions increased anxiety, fatigue and decreased vigor (p < 0.05). CONCLUSIONS: Acute exercise bouts are associated with negative changes in anxiety and mood, and with increases in hunger in obese adolescents.     

Single vs multivessel treatment during primary angioplasty: results of the multicentre randomised HEpacoat™ for cuLPrit or multivessel stenting for Acute Myocardial Infarction (HELP AMI) Study

DESIGN: Prospective randomized, multicentre study. RATIONALE: Recanalisation of the culprit lesion is the main goal of primary angioplasty for acute myocardial infarction. With the exception of cardiogenic shock, staged procedures are performed in the presence of multivessel disease. The study hypothesis is that with modern non-thrombogenic stents (heparin coated) complete revascularization with multivessel treatment can be safely achieved during the primary angioplasty procedure with a lower need of subsequent revascularization procedures and at a lower cost. ENDPOINTS: PRIMARY: 12-month incidence of repeat revascularization (any revascularization, infarct related artery as well as non-infarct-related artery). SECONDARY: (1) in hospital repeat revascularization, reinfarction and death; (2) total hospital cost (including a 12 months follow-up period). METHODS: 69 patients with ST elevation Acute Myocardial Infarction (AMI), &lt;12 hours after symptoms onset, undergoing primary angioplasty, with documented multivessel disease and both culprit lesion and 1 to 3 other lesions suitable for stent implantation. Unbalanced randomization between culprit lesion treatment only ( n??=?17) and complete multivessel treatment (n?=?52, with 71 additional lesions treated).RESULTS: The two groups were well balanced in terms of clinical characteristics, number of diseased vessels and angiographic characteristics of the culprit lesion. In the complete multivessel treatment group 2.36?±?0.64 lesions per patient were treated using 2.73?±?0.78 heparin coated stents (1.00 lesions and 1.29?±?0.61 stents in the culprit treatment group, bothp?&lt;?0.001). The duration of the procedure increased from 53?±?21?min (culprit treatment group) to 69?±?32?min (p?=?0.032) and the amount of contrast used from 242?±?102?ml (culprit treatment group) to 341?± 163?ml (multivessel complete treatment),p?=?0.025. A similar low incidence of in-hospital major adverse cardiac events was observed in the 2 groups (0 and 3.8% in culprit and multivessel treatment groups,p?=?0.164). The increase in the incidence of new revascularisation in the culprit treatment group at 12 month follow-up was not significant (35 vs 17%,p?=?0.247) but was sufficient to compensate the initial higher in-hospital cost, with a similar 12 month hospital cost in the 2 groups (&euro;22 330?±?&euro;13 653 vs &euro;20 382?±?&euro;11 671,p?=?0.231).CONCLUSION: Multivessel treatment during primary PTCA was safe in this controlled trial. However, when only the culprit lesion was initially treated, the need for subsequent clinically driven revascularization remained low and no clinical or economical advantages were obtainable with a more aggressive initial approach. In clinical practice, a staged approach to multivessel treatment during primary angioplasty avoids to treat unnecessarily non clinically relevant lesions. (Int J Cardiovasc Intervent 2004; 6: 128-133)     

Nutritional risk among Brazilian children 2 to 6 years old: A multicenter study

ObjectiveTo estimate the nutritional risk in children 2 to 6 y old.MethodsThe sample consisted of 3058 children enrolled in public and private schools in nine Brazilian cities. The assessment of nutrient intake was based on 1-d data combining direct individual weighing of foods and a food diary. A second evaluation of food consumption was conducted in a subsample to estimate the usual intake.ResultsThere was low prevalence of inadequate intake of vitamin B6 (<0.001%), riboflavin (<0.001%), niacin (<0.001%), thiamin (<0.001%), folate (<0.001%), phosphorus (<0.1%), magnesium (<0.1%), iron (<0.5%), copper (<0.001%), zinc (<0.5%), and selenium (<0.001%). However, 22% of children younger than 4 y and 5% of children older than 4 y consumed fiber quantities larger than the adequate intake. Approximately 30% of the sample consumed more saturated fat than recommended. The prevalence of inadequate vitamin E intake ranged from 15% to 29%. More than 90% of the children had an inadequate vitamin D intake. In children older than 4 y, the prevalence of inadequate calcium intake was approximately 45%. Sodium intake was higher than the upper intake level in 90% of children younger than 4 y and 73% of children older than 4 y.ConclusionsThe prevalence of inadequate dietary intake was low for most nutrients. However, fiber, calcium, and vitamin D and E intakes were lower than recommended. Moreover, children consumed large amounts of sodium and saturated fat.