Clinical implication of monitoring rivaroxaban and apixaban by using anti-factor Xa assay in patients with non-valvular atrial fibrillation

AbstractBackgroundAlthough patients taking non-vitamin K antagonist oral anticoagulants (NOACs) do not require routine coagulation monitoring, high-risk patients require monitoring to assess pharmacodynamics.MethodsWe measured (1) anti-factor Xa activity (AXA), using chromogenic assay with the HemosIL Liquid Heparin kit, (2) prothrombin time (PT), and (3) activated partial thromboplastin time (aPTT) in 188 blood samples from 70 patients with non-valvular atrial fibrillation, of whom 36 received rivaroxaban once daily and 34 received apixaban twice daily.ResultsAfter the rivaroxaban therapy, AXA ranged from 0 to 3.65IU/mL; PT, from 9.6 to 44.5s; and APTT, from 19.3 to 69.7s. After the apixaban therapy, AXA ranged from 0.02 to 3.18IU/mL; PT, from 10.2 to 20.8s; and APTT, from 21.8 to 59.8s. At peak time, the AXA of patients who received rivaroxaban and apixaban were almost the same (2.08±0.91IU/mL vs. 1.71±0.57IU/mL), but the PT and APTT of patients who received rivaroxaban were more prolonged than those of patients who received apixaban (18.1±5.6s vs. 13.8±0.9s, p<0.001 and 40.9±7.3s vs. 35.5±7.5s, p<0.01, respectively). At trough time, the AXA and PT of patients who received rivaroxaban were respectively lower and shorter than those of patients who received apixaban (0.28±0.31IU/mL vs. 1.04±0.72IU/mL, p<0.001 and 11.9±2.0s vs. 13.7±2.4s, p<0.01, respectively), but the APTT of patients who received rivaroxaban and apixaban did not significantly differ (32.3±4.3s vs. 34.3±3.8s).ConclusionsMeasurement of AXA might be useful to assess the pharmacodynamics of high-risk patients, such as high age, low body weight, and/or low renal function, and to assess the intensity of anticoagulation by using different methods of administration, such as crushed tablet via the nasogastric tube

Spectral Analysis of Epicardial 60-lead Electrograms in Dogs during Acute Myocardial Ischemia

急性心筋虚血が心全サイクルにわたる各周波数の要素に及ぼす効果を分析した.7犬について冠動脈閉塞前後に60誘導心外膜心電図を記録し,単一平均と高速フーリエ変換を行い,逆変換を5周波数レンジで行った.心サイクル中の再構築した波形の絶対値を積分し,フィルターQRST面積地図として表示した.心筋虚血では初期QRSにおいてのみ低周波数(0-25Hz)の要素が有意に感じるが,これら要素はQRSの後半部とSTで著明に増加した.逆に心筋虚血はQRSの中間部の早期に中および高周波(25-250Hz)の要素を有意に減じるが,終末期QRSでの高周波数(80-250Hz)の要素を著明に増加した急性心筋虚血が心全サイクルにわたる各周波数の要素に及ぼす効果を分析した.7犬について冠動脈閉塞前後に60誘導心外膜心電図を記録し,単一平均と高速フーリエ変換を行い,逆変換を5周波数レンジで行った.心サイクル中の再構築した波形の絶対値を積分し,フィルターQRST面積地図として表示した.心筋虚血では初期QRSにおいてのみ低周波数(0-25Hz)の要素が有意に感じるが,これら要素はQRSの後半部とSTで著明に増加した.逆に心筋虚血はQRSの中間部の早期に中および高周波(25-250Hz)の要素を有意に減じるが,終末期QRSでの高周波数(80-250Hz)の要素を著明に増加した急性心筋虚血が心全サイクルにわたる各周波数の要素に及ぼす効果を分析した.7犬について冠動脈閉塞前後に60誘導心外膜心電図を記録し,単一平均と高速フーリエ変換を行い,逆変換を5周波数レンジで行った.心サイクル中の再構築した波形の絶対値を積分し,フィルターQRST面積地図として表示した.心筋虚血では初期QRSにおいてのみ低周波数(0-25Hz)の要素が有意に感じるが,これら要素はQRSの後半部とSTで著明に増加した.逆に心筋虚血はQRSの中間部の早期に中および高周波(25-250Hz)の要素を有意に減じるが,終末期QRSでの高周波数(80-250Hz)の要素を著明に増加した急性心筋虚血が心全サイクルにわたる各周波数の要素に及ぼす効果を分析した.7犬について冠動脈閉塞前後に60誘導心外膜心電図を記録し,単一平均と高速フーリエ変換を行い,逆変換を5周波数レンジで行った.心サイクル中の再構築した波形の絶対値を積分し,フィルターQRST面積地図として表示した.心筋虚血では初期QRSにおいてのみ低周波数(0-25Hz)の要素が有意に感じるが,これら要素はQRSの後半部とSTで著明に増加した.逆に心筋虚血はQRSの中間部の早期に中および高周波(25-250Hz)の要素を有意に減じるが,終末期QRSでの高周波数(80-250Hz)の要素を著明に増加し

Juvenile Bow Hunter’s Stroke without Hemodynamic Changes

Bow hunter’s stroke (BHS) is a cerebrovascular disease caused by occlusion of the vertebral artery (VA) on head rotation. BHS is generally associated with hemodynamic changes, often leading to vertebrobasilar insufficiency symptoms, such as vertigo and faintness. Although artery-to-artery embolism has also been proposed as an underlying mechanism, it remains controversial. This report documents a case of BHS without hemodynamic changes. We describe a 26-year-old male patient who had VA occlusion on head rotation and repetitive infarction of thalami. He had an anomalous bypass of the VA and therefore no symptomatic hemodynamic changes. Thus, non-hemodynamic BHS should be considered in juvenile patients with vertebrobasilar stroke

Serum alpha-fetoprotein levels in healthy Japanese adults.

With advances in lectin affinity electrophoresis of alpha-fetoprotein (AFP), the detection of significant changes in serum AFP at low levels in cirrhotics has become important for early detection of hepatocellular carcinoma. Serum AFP levels of 616 healthy individuals without abnormal liver function tests or virus markers of hepatitis B and C were determined by enzyme immunoassay with IMx-AFP Dainapack using automated IMx apparatus set at twice the ordinary sensitivity and compared with those of 241 individuals with abnormal liver function tests and/or positive hepatitis virus markers. The coefficient of variation in this assay was less than 10% at AFP levels as low as 0.2 ng/ml with a lower detection limit of 0.1 ng/ml. The AFP level of healthy population showed a Gaussian distribution curve after logarithmic transformation with a median and 2.5-97.5 percentile reference range of 2.2 (0.6-5.6) ng/ml. There was no significant difference in the AFP level between males and females. Individuals with abnormal liver function tests alone showed no significant increase in serum AFP unless they were associated with positive hepatitis virus markers. </p

A novel approach for the endothelialization of xenogeneic decellularized vascular tissues by human cells utilizing surface modification and dynamic culture

Decellularized xenogeneic vascular grafts can be used in revascularization surgeries. We have developed decellularization methods using high hydrostatic pressure (HHP), which preserves the extracellular structure. Here, we attempted ex vivo endothelialization of HHP-decellularized xenogeneic tissues using human endothelial cells (ECs) to prevent clot formation against human blood. Slices of porcine aortic endothelium were decellularized using HHP and coated with gelatin. Human umbilical vein ECs were directly seeded and cultured under dynamic flow or static conditions for 14 days. Dynamic flow cultures tend to demonstrate higher cell coverage. We then coated the tissues with the E8 fragment of human laminin-411 (hL411), which has high affinity for ECs, and found that Dynamic/hL411showed high area coverage, almost reaching 100% (Dynamic/Gelatin vs Dynamic/hL411; 58.7 ± 11.4 vs 97.5 ± 1.9%, P = 0.0017). Immunostaining revealed sufficient endothelial cell coverage as a single cell layer in Dynamic/hL411. A clot formation assay using human whole blood showed low clot formation in Dynamic/hL411, almost similar to that in the negative control, polytetrafluoroethylene. Surface modification of HHP-decellularized xenogeneic endothelial tissues combined with dynamic culture achieved sufficient ex vivo endothelialization along with prevention of clot formation, indicating their potential for clinical use as vascular grafts in the future

Seaweed intake and blood pressure levels in healthy pre-school Japanese children

<p>Abstract</p> <p>Background</p> <p>Few studies have examined whether dietary factors might affect blood pressure in children. We purposed to investigate whether seaweed intake is associated with blood pressure level among Japanese preschool children.</p> <p>Methods</p> <p>The design of the study was cross-sectional and it was conducted in autumn 2006. Subjects were healthy preschoolers aged 3-6 years in Aichi, Japan. Blood pressure and pulse were measured once by an automated sphygmomanometer, which uses oscillometric methods. Dietary data, including seaweed intake, were assessed using 3-day dietary records covering 2 consecutive weekdays and 1 weekend day. Of a total of 533 children, 459 (86.1 percent) agreed to be enrolled in our study. Finally, blood pressure measurement, complete dietary records and parent-reported height and weight were obtained for 223 boys and 194 girls.</p> <p>Results</p> <p>When we examined Spearman's correlation coefficients, seaweed intake was significantly negatively related to systolic blood pressure in girls (<it>P </it>= 0.008). In the one-way analysis of covariance for blood pressure and pulse after adjustments for age and BMI, the boys with the lowest, middle and highest tertiles of seaweed intake had diastolic blood pressure readings of 62.8, 59.3 and 59.6 mmHg, respectively (<it>P </it>= 0.11, trend <it>P </it>= 0.038). Girls with higher seaweed intake had significantly lower systolic blood pressure readings (102.4, 99.2 and 96.9 mmHg for girls with the lowest, middle and highest tertiles of seaweed intake, respectively; <it>P </it>= 0.037, trend <it>P </it>= 0.030).</p> <p>Conclusion</p> <p>Our study showed that seaweed intake was negatively related to diastolic blood pressure in boys and to systolic blood pressure in girls. This suggests that seaweed might have beneficial effects on blood pressure among children.</p

Protein oxidation mediated by heme-induced active site conversion specific for heme-regulated transcription factor, iron response regulator

The Bradyrhizobium japonicum transcriptional regulator Irr (iron response regulator) is a key regulator of the iron homeostasis, which is degraded in response to heme binding via a mechanism that involves oxidative modification of the protein. Here, we show that heme-bound Irr activates O-2 to form highly reactive oxygen species (ROS) with the "active site conversion" from heme iron to non-heme iron to degrade itself. In the presence of heme and reductant, the ROS scavenging experiments show that Irr generates H2O2 from O-2 as found for other hemoproteins, but H2O2 is less effective in oxidizing the peptide, and further activation of H2O2 is suggested. Interestingly, we find a time-dependent decrease of the intensity of the Soret band and appearance of the characteristic EPR signal at g = 4.3 during the oxidation, showing the heme degradation and the successive formation of a non-heme iron site. Together with the mutational studies, we here propose a novel "two-step self-oxidative modification" mechanism, during which O-2 is activated to form H2O2 at the heme regulatory motif (HRM) site and the generated H2O2 is further converted into more reactive species such as OH at the non-heme iron site in the His-cluster region formed by the active site conversion