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De Kam P.-J.,Neuros | Hou J.,TEDA International Cardiovascular Hospital | Wang Z.,MSDBeijing | Van Den Heuvel M.,MSD
International Journal of Clinical Pharmacology and Therapeutics | Year: 2015

Objective: Elimination of sugammadex occurs predominantly via the kidneys, with the majority of the drug excreted unchanged in the urine. To date, most studies with sugammadex have been performed in non-Asian populations. The objectives of this open-label study were to determine the pharmacokinetics (PK) and safety of single-dose sugammadex (16 mg/kg) in healthy Chinese adult volunteers. Methods: 12 Chinese subjects (6 male; 6 female) received intravenous sugammadex (16 mg/kg) as a 10-second bolus infusion. Blood samples were collected pre-sugammadex and at regular intervals up to 24 hours post-sugammadex for PK assessment. Safety was assessed via AEs, vital signs, electrocardiogram, and laboratory parameters. Results: Following sugammadex 16 mg/kg infusion, peak sugammadex concentration was 197 μg/mL, clearance was 99.7 mL/min, and apparent volume of distribution at equilibrium was 10.5 L. Plasma sugammadex concentrations showed a polyexponential decline over time, with an overall geometric mean (CV%) terminal half-life of 145 minutes (17.9%) (139 minutes (17.7%) for males; 152 minutes (18.6%) for females). No influence of gender on the PK of sugammadex was observed. Three subjects experienced an adverse events (AE) (dysgeusia of mild intensity), which was considered possibly or probably related to sugammadex. There were no clinically significant changes in vital signs, electrocardiography or laboratory parameters. Conclusion: PK of sugammadex (16 mg/kg) was characterized in healthy Chinese subjects. Overall between-subject variability on clearance and apparent volume of distribution was ∼ 10%. Sugammadex was generally well tolerated. ©2015 Dustri-Verlag Dr. K. Feistle. Source

Zhao J.,Zhengzhou University | Cheng Z.,Zhengzhou University | Quan X.,Zhengzhou University | Zhao Z.,Zhengzhou University | And 2 more authors.
Journal of Surgical Research | Year: 2014

Background The transmural biodegradable polycaprolactone/poly(D,L-lactic/ glycolic acid) (PCL/PLGA) scaffold is a promising modality for diffuse coronary atherosclerosis cases that are not suitable for bypass grafting. The purpose of this study was to evaluate the long-term performance of the PCL/PLGA scaffold in vivo in the setting of polymer and heparin degradation. Materials and methods After mechanical drilling through the ventricular wall was performed in the whole ventricular wall, two scaffolds were implanted into the ventricular wall. Animals were grouped into the single drilling group (SD group), the blank scaffold group (BS group), and the heparinized scaffold group (HS group) and were allowed to survived for 6 mo. Next, the patency and integrity of the scaffolds were evaluated by echocardiography and 3D-DOCTOR software. Endothelium coverage of the lumen was evaluated by scanning electron microscopy. Neovessels and collagen fiber within the scaffolds were identified by histologic staining. Metabolite production of prostacyclin (PGI2) and thromboxane A 2 (TXA2) in the plasma was measured by an enzyme-linked immunosorbent assay. The expression levels of PGI2 synthase and cyclooxygenase 2 (COX-2) involved in PGI2 production and COX-1 involved in TXA2 production were measured by Western blot analysis. Results The heparinized scaffolds were patent for up to 6 mo and the lumen was covered with confluent endothelial cells. Histologic staining revealed collagen fiber remodeling and reconstruction of the neovascular network immediately surrounding the lumen. The expression of PGI2 synthase and COX-2 in the HS group was significantly higher compared with the SD and BS groups (P < 0.01). The expression of COX-1 was similar in the three groups (P > 0.05). Consistent with synthetase expression, a PGI2 metabolite (6-keto-PGF1a) also showed a significant increase in the HS group relative to the SD and BS groups (P = 0.021 and P = 0.015, respectively). Concomitantly, as a PGI2 antagonist, the TXA2 metabolite (TXB2) did not exhibit a significant difference among the three groups (P = 0.17). Conclusions Despite polymer and heparin degradation, the scaffold could continuously maintain the structural integrity and lumen patency for up to 6 mo by reinforcement of host collagen fiber and the balance of PGI 2/TXA2. © 2014 Elsevier Inc. All rights reserved. Source

Yang Q.,Chinese University of Hong Kong | He G.-W.,TEDA International Cardiovascular Hospital | He G.-W.,Hangzhou Normal University | Underwood M.J.,Chinese University of Hong Kong | Yu C.-M.,Chinese University of Hong Kong
American Journal of Translational Research | Year: 2016

Ischemia/reperfusion (I/R) injury is a major cause of myocardial damage. Despite continuous efforts, minimizing I/R injury still represents a great challenge in standard medical treatments of ischemic heart disease, i.e., thrombolytic therapy, primary percutaneous coronary intervention, and coronary arterial bypass grafting. Development of effective interventions and strategies to prevent or reduce myocardial I/R injury is therefore of great clinical significance. Endothelial dysfunction plays a significant role in myocardial I/R injury, which renders endothelial cells an attractive target for postischemic myocardial protection. The rapidly evolving knowledge of the mechanisms of endothelial I/R injury helps broaden perspective for future development of novel strategies targeting endothelium for alleviating myocardial I/R damage. This review provides a comprehensive summary of the cellular and molecular mechanisms of endothelial I/R injury. Current perspectives and future directions for developing endothelium targeting therapeutics for postischemic myocardial protection are further discussed. © 2016, E-Century Publishing Corporation. All rights reserved. Source

Chen J.,Tianjin Medical University | Sun F.,Tianjin Medical University | Fu J.,Wuhan Medical Care Center for Women and Children | Zhang H.,TEDA International Cardiovascular Hospital
Pediatric Cardiology | Year: 2015

As a transcription factor mainly expressed in cardiovascular system, T-box 20 (TBX20) plays an important role in embryonic cardiovascular system development and adult heart function. Previous studies have identified associations of two SNPs in the T-box DNA-binding domain of TBX20 with congenital heart disease (CHD) in two Caucasian families, but the associations of TBX20 mutations underlying the more common populations with CHD remain to be uncovered. In this study, 25 unrelated Chinese Han neonates with CHD and 25 healthy children as controls were investigated for TBX20 mutations. SNP genotyping was performed by PCR-DNA sequencing. The selected SNPs were well genotyped and SNP rs3999941 was found to be strongly associated with CHD (p = 0.007). The minor allele of rs3999941 showed a high-risk factor for CHD (OR 4.24; 95 % CI 1.41–12.71). Besides, we found a new SNP site located at the 657th nucleotide of the exon 5 of TBX20 gene which may also be associated with CHD, c.657A>C. The frequency was significantly different between two groups (p = 0.011), the minor allele of SNP c.657A>C also showed a risk factor for CHD (OR 2.56; 95 % CI 1.02–6.46). These findings suggested that the TC genotype of SNP rs3999941 and AC genotype of the new SNP c.657A>C in the TBX20 gene may be risk factors for CHD and thus screening of these SNPs may have some implications in the prevention and treatment of CHD in Han Chinese children. © 2014, Springer Science+Business Media New York. Source

Zhang L.R.,TEDA International Cardiovascular Hospital
Zhonghua xin xue guan bing za zhi | Year: 2011

To observe the coronary vessel lumen diameter and bifurcation angle in subjects with normal CT coronary angiography (CTCA) imaging. 64-row CT coronary angiography imaging from 526 adult people with excellent image quality and normal vascular image were analyzed in this study. The lumen diameter from the origin to distal with 2 mm lumen of left main coronary artery (LM), anterior descending branch (LAD), left circumflex branch (LCX) and right coronary artery (RCA) was measured at 1 cm interval in CPR image. The vascular tapered ratio was calculated. The bifurcation angle in the diagonal branch, obtuse marginal branch, posterior descending branch, acute marginal branch as well as the origin diameter was also measured in VR image. The LAD average length was 13 cm and lumen diameter was 3.92 mm at origin and 2.10 mm at distal. The average decremented ratio of LAD was 7.7% (male 7.0%, female 8.4%). The maximal decremented ratio 8.0% - 10.0% occurred at 3 - 5 cm apart from the origin of LAD. The LCX average length was 13 cm and lumen diameter was 3.57 mm at origin and 2.10 mm at distal. The average decremented ratio of LCX was 9.7% (male 9.6%, female 9.7%). Lumen decremented ratio was less than 3.0% between origin and proximal 3 cm and 8.3% - 10.7% in the rest portion of the LCX. The RCA average length was 18 cm and lumen diameter was 3.97 mm at origin and 2.15 mm at distal. The average decremented ratio of RCA was 5.1% (male 4.9%, female 5.3%). The decremented ratio of RCR was less than 4.0% between origin and proximal 10 cm and 6.1% - 15.2% in the rest portion. The bifurcation angle was 50, 55, 66 and 76 degree for LAD with diagonal branch, LCX with obtuse marginal branch, RCA with posterior descending branch and RCA with obtuse marginal branch respectively. Coronary artery length, lumen diameter and decremented ratio as well as bifurcation angel could be identified in 64 row CTCA image in vivo. This information could help us to understand the in vivo coronary artery anatomy. Source

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