Vorapaxar may be superior to currently recommended antiplatelet strategies and should be tested as a monotherapy in a randomized outcome-driven secondary stroke prevention trial.
Background:
Conventional anticoagulation with warfarin remains the cornerstone strategy for numerous preventive strategies. It is established that Asian patients require lower warfarin doses than Caucasians potentially attributing to the genetic polymorphism (GP) differences.
Areas of Uncertainty:
The impact of GP on optimal warfarin dose (OWD) in Koreans is unclear when compared with other ethnicities. It is also not well established whether GP linked to OWD in Korean patients to the similar extend as in Chinese, Japanese, and Caucasians.
Data Sources:
Single-center prospective observational study in Koreans, matched with historic cohorts of other ethnicities.
Therapeutic Advances:
Clinical characteristics, concomitant medications, OWD, international normalized ratio, and VKORC1, CYP2C9, and CYP4F2 GPs were assessed in consecutive Korean patients. The OWD was defined when patient's international normalized ratio was within target range for at least 3 consecutive times separated by 1 week. We included 133 (mean age 62.6 ± 12.1 years, 49% males) warfarin-treated patients of Korean descend. The mean OWD was 3.30 ± 1.34 (range: 1–9) mg/d. Homozygous wild-type patients required lower OWD (3.1 ± 1.1 mg/d vs. 4.7 ± 1.8 mg/d, P < 0.001) for VKORC1 and higher OWD for both CYP2C9 (3.4 ± 1.3 mg/d vs. 2.3 ± 1.1 mg/d, P = 0.002) and CYP4F2 (3.0 ± 1.2 mg/d vs. 3.4 ± 1.3 mg/d vs. 4.0 ± 1.7 mg/d, P = 0.033) than those carrying heterozygote genes.
Conclusions:
Korean patients exhibit different VKORC1, CYP2C9, and CYP4F2 profiles impacting lower OWD in Eastern Asians than required in Caucasians. Universal international OWD guidelines may consider patient ethnicity as a confounder; however, this hypothesis needs further clarification.
Background:
Adipose tissue has been identified as a source of multipotent cells that have the capacity to differentiate into cardiac myocytes, endothelial cells, similar to bone marrow cells. We sought to investigate the effect of adipose tissue-derived stromal cells (ADSCs) therapy on cardiac contractility and remodeling in C57BL/6 mouse model of acute myocardial infarction (AMI).
Materials and Methods:
Total 30 adult male C58BL/6 mice (12 weeks of age, 28~30g body weight) were used for the study. Mice were randomized into two groups (MI + media, n = 15 and MI + ADSCs, n= 15) after producing AMI by ligation of left anterior descending coronary artery. Intramyocardial injection of 1 × 10
6
ADSCs cells was compared to the injection of media alone. Ten animals were excluded from further analyses because of death. Most of them died 7 to 10 days after AMI, a mouse died duing surgical procedure following LAD ligation. All survived mice (n = 20) were received echocardiograpic analysis before and 2 weeks after cell transplantation, and then sacrificed for histologic analysis.
Results: The fractional shortening and left ventricular ejection fraction improved significantly in ADSCs transplant group at 2 weeks compared to control group (
20.9
± 3.48% vs 29.9 ± 8.6%,
p
=
0.006
and 46.4 ± 7.6% vs 63.1 ± 12.8%,
p
=
0.002
). Left ventricular end dialstolic dimension in ADSCs transplant group showed a little decrease from 4.65 ± 0.63 mm (control) to 4.14 ± 0.53 mm (ADSC), but there was no statistical difference (
p
< 0.072), whereas left ventricle end-systolic diameter decreased significantly in cell transplantation group (
p
< 0.05). Also, there were significant difference in injury size, infarct area, wall thickness or scar formation in ADSC group. In histochemical analysis, ADSCs have been shown to migrate into the injured sites and to integrate into the scar areas with some of transplanted ADSCs expressing endothelial marker.
Conclusion:
ADSCs improved left ventricular function and showed favorable effect on remodeling. They could be a good candidate for the source of cell therapy after myocardial injury.
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