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Biomedical subjects

Hao Wang

Publications and source records attributed to Hao Wang.

At least 73 records · Page 4Linked to original sources

Mechanisms of angiotensin II-dependent progression to heart failure.

Up-regulation of angiotensin II (AII) signalling plays an important role in the pathogenesis of cardiac hypertrophy and failure as evidenced by the efficacy of AII receptor blockers or inhibitors of AII biosynthesis in reversing ventricular hypertrophy and preventing human heart failure. The mechanisms underlying AII action in the heart remain undefined. Myocardial-specific expression of the AII type 1 receptor (AT1R) in mice is sufficient for inducing progressive myocyte hypertrophy and cardiac remodelling leading to adult heart failure with a disease progression course reminiscent of work overload-induced human heart failure. We examined the functional, structural and genetic changes associated with disease progression in this model. The results reveal that AT1R-dependent interaction between myocytes and non-myocytes is critical in cardiac remodelling. At the level of cardiomyocytes, decreased mitochondrial function is one of the earliest events of AII action leading to mitochondrial depletion and increased apoptosis. Up-regulation of cardiac Bcl-2 prevents mitochondrial deterioration, cardiomyocyte loss and pathologic remodelling. Importantly, Bcl-2 completely rescues premature death due to heart failure and maintains the 'compensated' state. The data suggest that targeting Bcl-2 or interfering with mitochondrial dysfunction may offer new therapeutic opportunities for preventing transition from compensated hypertrophy to heart failure.

Angiotensin II↗

A double-blind randomized trial of adefovir dipivoxil in Chinese subjects with HBeAg-positive chronic hepatitis B.

Four hundred and eighty Chinese subjects with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) were enrolled in a multicenter, double-blind, randomized, placebo-controlled study of adefovir dipivoxil (ADV) 10 mg once daily. There was a significant difference in reduction of serum hepatitis B virus (HBV) DNA after 12 weeks between subjects who received ADV and those who received the placebo (3.4 and 0.1 log10 copies/mL, respectively, P < .001). Further reductions in serum HBV DNA and increases in the proportion of subjects with an HBV DNA level of at most 10(5) copies/mL, with HBV DNA undetectable, and with ALT normalization were observed in ADV-treated subjects at week 52 (median HBV DNA reduction of 4.5 log(10) copies/mL, 67% with HBV DNA <or= 10(5) copies/mL, 28% with HBV DNA undetectable, and 79% with ALT normalization). Subjects who initially received ADV lost some treatment benefit after being rerandomized to the placebo in week 40. Subjects with YMDD mutant HBV at baseline had virological, biochemical, and serological responses to treatment that were similar to those of subjects with wild-type HBV. The incidence of clinically adverse events was similar in nature and severity between the treatment groups, and there was no evidence of renal toxicity. No adefovir-related HBV mutations were identified. In conclusion, treatment with ADV 10 mg daily over 52 weeks was safe and effective in Chinese subjects with HBeAg-positive CHB and did not lead to the emergence of drug resistance. The study is continuing for an additional 4 years with all subjects on open-label ADV 10 mg daily.

Adenine↗

CD40 ligand increases expression of its receptor CD40 in human coronary artery endothelial cells.

BACKGROUND: Recently, CD40 ligand (CD40L) and its receptor CD40 have been implicated in atherosclerosis. Clinical data showed that elevated CD40L levels are associated with a high risk of cardiovascular events. The aim of this study was to investigate whether CD40L could affect the expression of its membrane receptor CD40 as a feedback mechanism by which CD40L could enhance its functions in human coronary artery endothelial cells (HCAECs). METHODS: The HCAECs were treated with human soluble CD40L, and the messenger RNA (mRNA) and protein levels of CD40 were determined by real-time polymerase chain reaction and Western blot analysis, respectively. The specific effect of CD40L was confirmed by a blocking experiment with antibody against CD40L. Involvements of oxidative stress and mitogen-activated protein kinases (MAPKs) were also studied with antioxidant seleno-L-methionine (SeMet) and MAPK inhibitors such as extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor. RESULTS: When HCAECs were cultured with CD40L (5 microg/mL) for 24 hours, CD40 mRNA levels were increased by 79% compared with controls (P < .05). Similarly, Western blot analysis showed an 80% increase in CD40 protein levels (P < .05). The CD40L-induced increase in CD40 mRNA levels were blocked specifically by anti-CD40L antibody. Antioxidant SeMet and specific ERK1/2 inhibitor (PD98059) also effectively blocked CD40L-induced CD40 mRNA increase. CONCLUSIONS: These data demonstrate that clinically relevant concentration of CD40L increased the expression of its receptor CD40 in HCAECs. The CD40L-induced upregulation of CD40 may be mediated by oxidative stress and ERK1/2 activation. This study suggests a new mechanism by which CD40L could enhance its biologic functions in the vascular system and contribute to endothelial dysfunction and vascular disease.

Antioxidants↗

Secretoneurin increases monolayer permeability in human coronary artery endothelial cells.

BACKGROUND: Secretoneurin (SN), a novel neuropeptide, may play a role in inflammation in the vascular system. However, the interaction between SN and endothelial cells is largely unknown. This study's objective is to investigate the effects of SN on endothelial permeability and its associated molecular mechanisms in human coronary artery endothelial cells (HCAECs). METHODS: HCAECs were treated with SN. Monolayer permeability was assayed with a transwell system and a Texas Red-labeled dextran tracer. The mRNA and protein levels of endothelial junctional molecules were determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. Superoxide anion was determined by fluorescent dye dihydroethidium-based flow cytometry detection. Mitogen-activated protein kinase (MAPK) activation was determined by Bio-Plex immunoassay. RESULTS: HCAECs were treated with SN (15, 30, and 60 ng/ml) for 24 hours and showed a significant increase of monolayer permeability by 12%, 33%, and 47%, respectively, compared with controls (P < 0.05). SN-treated cells showed a significant reduction of zonula occludens-1 (ZO-1) and occludin at both mRNA and protein levels (P < 0.05). In addition, SN significantly increased superoxide anion in HCAECs (P < 0.05). Furthermore, SN activated MAPKs (JNK and ERK1/2) but not p38. Both antioxidant seleno-L-methionine (SeMet) and specific inhibitors of JNK and ERK1/2 effectively blocked SN-induced monolayer permeability increase in HCAECs. CONCLUSIONS: SN significantly increases monolayer permeability and reduces the expression of ZO-1 and occludin through oxidative stress and the activation of JNK and ERK1/2 in HCAECs. This study provides direct evidence that SN impairs endothelial barrier function.

Capillary Permeability↗

Stereospecific formation of interstrand carbinolamine DNA cross-links by crotonaldehyde- and acetaldehyde-derived alpha-CH3-gamma-OH-1,N2-propano-2'-deoxyguanosine adducts in the 5'-CpG-3' sequence.

The crotonaldehyde- and acetaldehyde-derived R- and S-alpha-CH3-gamma-OH-1,N2-propanodeoxyguanosine adducts were monitored in single-stranded and duplex oligodeoxynucleotides using NMR spectroscopy. In both instances, the cis and trans diastereomers of the alpha-CH3 and gamma-OH groups underwent slow exchange, with the trans diastereomers being favored. In single-stranded oligodeoxynucleotides, the aldehyde intermediates were not detected spectroscopically, but their presence was revealed through the formation of N-terminal conjugates with the tetrapeptide KWKK. When annealed into 5'-d(GCTAGCXAGTCC)-3'.5'-d(GGACTCYCTAGC)-3' containing the 5'-CpG-3' sequence context (X = R- or S-alpha-CH3-gamma-13C-OH-PdG; Y = 15N2-dG) at pH 7, partial opening of the R- or S-alpha-CH3-gamma-13C-OH-PdG adducts to the corresponding N2-(3-oxo-1-methyl-propyl)-dG aldehydes was observed at temperatures below the T(m) of the duplexes. These aldehydes equilibrated with their geminal diol hydrates; higher temperatures favored the aldehydes. When annealed opposite T, the S-alpha-CH3-gamma-13C-OH-PdG adduct was stable. At 37 degrees C, an interstrand DNA cross-link was observed spectroscopically only for the R-alpha-CH3-gamma-OH-PdG adduct. Molecular modeling predicted that the interstrand cross-link formed by the R-alpha-CH3-gamma-OH-PdG adduct introduced less disruption into the duplex structure than did the cross-link arising from the S-alpha-CH3-gamma-OH-PdG adduct, due to differing orientations of the R- and S-CH3 groups. Modeling also predicted that the alpha-methyl group of the aldehyde arising from the R-alpha-CH3-gamma-OH-PdG adduct is oriented in the 3'-direction in the minor groove, facilitating cross-linking. In contrast, the alpha-methyl group of the aldehyde arising from the S-alpha-CH3-gamma-OH-PdG adduct is oriented in the 5'-direction within the minor groove, potentially hindering cross-linking. NMR revealed that for the R-alpha-CH3-gamma-OH-PdG adduct, the carbinolamine form of the cross-link was favored in duplex DNA with the imine (Schiff base) form of the cross-link remaining below the level of spectroscopic detection. Molecular modeling predicted that the carbinolamine linkage maintained Watson-Crick hydrogen bonding at both of the tandem C.G base pairs. Dehydration of the carbinolamine cross-link to an imine, or cyclization of the latter to form a pyrimidopurinone cross-link, required disruption of Watson-Crick hydrogen bonding at one or both of the cross-linked base pairs.

Acetaldehyde↗

Orientation of the crotonaldehyde-derived N2-[3-Oxo-1(S)-methyl-propyl]-dG DNA adduct hinders interstrand cross-link formation in the 5'-CpG-3' sequence.

The conformation of the crotonaldehyde-derived N(2)-[3-oxo-1(S)-methyl-propyl]-dG adduct in the oligodeoxynucleotide 5'-d(G(1)C(2)T(3)A(4)G(5)C(6)X(7)A(8)G(9)T(10)C(11)C(12))-3'.5'-d(G(13)G(14)A(15)C(16)T(17)C(18)G(19)C(20)T(21)A(22)G(23)C(2)(4))-3', where X = N(2)-[3-oxo-1(S)-methyl-propyl]-dG, is reported. This adduct arises from opening of the cyclic N(2)-(S-alpha-CH(3)-gamma-OH-1,N(2)-propano-2')-dG adduct when placed opposite dC in duplex DNA. This oligodeoxynucleotide contains the 5'-CpG-3' sequence in which the N(2)-(R-alpha-CH(3)-gamma-OH-1,N(2)-propano-2')-dG but not the N(2)-(S-alpha-CH(3)-gamma-OH-1,N(2)-propano-2')-dG adduct preferentially formed an interstrand carbinolamine cross-link [Kozekov, I. D., Nechev, L. V., Moseley, M. S., Harris, C. M., Rizzo, C. J., Stone, M. P., and Harris, T. M. (2003) J. Am. Chem. Soc. 125, 50-61; Cho, Y.-J., Wang, H., Kozekov, I. D., Kurtz, A. J., Jacob, J., Voehler, M., Smith, J., Harris, T. M., Lloyd, R. S., Rizzo, C. J., and Stone, M. P. (2006) Chem. Res. Toxicol. 19, 195-208]. Analysis of (1)H NOE data, chemical shift perturbations, and deoxyribose pseudorotations and backbone torsion angles suggested the presence of a stable and ordered DNA conformation at pH 9.3 and 30 degrees C, with minimal conformational perturbation. The spectral line widths of the adduct protons were comparable to those of the oligodeoxynucleotide, suggesting that the correlation times of these protons were similar to those of the overall duplex. The crotonaldehydic-derived methyl protons showed NOEs in the 5'-direction to C(18) H1', G(19) H1', and G(19) H4' in the complementary strand of the duplex. The aldehyde proton of the adduct exhibited NOEs in the 3'-direction to A(8) H1' and A(8) H4' in the modified strand. All of these NOEs involved DNA protons facing the minor groove. Molecular dynamics calculations, restrained by distances and torsion angles derived from the NMR data, revealed that within the minor groove, the aldehyde of the N(2)-[3-oxo-1(S)-methyl-propyl]-dG adduct oriented in the 3'-direction, while the 1(S) methyl group oriented in the 5'-direction. This positioned the aldehyde distal to the G(19) exocyclic amine and provided a rationale as to why the N(2)-(S-alpha-CH(3)-gamma-OH-1,N(2)-propano-2')-dG adduct generated interstrand cross-links less efficiently than did the N(2)-(R-alpha-CH(3)-gamma-OH-1,N(2)-propano-2')-dG adduct.

Aldehydes↗

Site-specific synthesis of oligonucleotides containing malondialdehyde adducts of deoxyguanosine and deoxyadenosine via a postsynthetic modification strategy.

Malondialdehyde (MDA) and its reactive equivalent, base propenal, are products of oxidative damage to lipids and DNA, respectively; they are mutagenic in bacterial and mammalian systems, and MDA is carcinogenic in rats. MDA adducts of deoxyguanosine (M1dG), deoxyadenosine (OPdA), and deoxycytidine (OPdC) have been characterized. We have developed site-specific syntheses of M1dG and OPdA adducted oligonucleotides that rely on a postsynthetic modification strategy. This work provides an alternative route to the M1dG adducted oligonucleotide and, to date, the only viable strategy for the site-specific synthesis of OPdA-modified oligonucleotides. The stability of the modified oligonucleotides was examined by UV thermal melting studies (Tm). In contrast to the M1dG adduct, OPdA caused very little change in the Tm.

Deoxyadenosines↗

Artificial matrix helps neonatal cardiomyocytes restore injured myocardium in rats.

The purpose of this study was to investigate whether an artificial matrix can help neonatal cardiomyocytes restore an injured heart in a rat model of myocardial infarction (MI). The left coronary arteries of female Sprague Dawley (SD) rats were ligated to create MI models. Ventricular cardiomyocytes from 1- to 3-day-old SD rats (both sexes) were isolated, cultured, and labeled. Three weeks after MI, the animals were randomized into four groups: (i) group cell plus matrix (n = 12); (ii) group cell (n = 12); (iii) group matrix (n = 12); and (iv) group control (n = 11). Four weeks after transplantation, echocardiography and the Langerdoff model were used to assess heart function. Immunohistochemical staining and polymerase chain reaction (PCR) were performed to track the implanted cardiomyocytes and detect the sex-determining region Y gene on the Y chromosome. Histology study and PCR showed that transplanted cardiomyocytes survived, formed condensed tissue, and produced connected protein in group cell plus matrix. Heart function assessment indicated transplantation of cardiomyocytes plus matrix preserved left ventricle wall thickness, fraction shortening, and end-systolic internal diameter most effectively.

Animals↗

Atomic force microscopy-based cell nanostructure for ligand-conjugated quantum dot endocytosis.

While it has been well demonstrated that quantum dots (QDs) play an important role in biological labeling both in vitro and in vivo, there is no report describing the cellular nanostructure basis of receptor-mediated endocytosis. Here, nanostructure evolution responses to the endocytosis of transferrin (Tf)-conjugated QDs were characterized by atomic force microscopy (AFM). AFM-based nanostructure analysis demonstrated that the Tf-conjugated QDs were specifically and tightly bound to the cell receptors and the nanostructure evolution is highly correlated with the cell membrane receptor-mediated transduction. Consistently, confocal microscopic and flow cytometry results have demonstrated the specificity and dynamic property of Tf-QD binding and internalization. We found that the internalization of Tf-QD is linearly related to time. Moreover, while the nanoparticles on the cell membrane increased, the endocytosis was still very active, suggesting that QD nanoparticles did not interfere sterically with the binding and function of receptors. Therefore, ligand-conjugated QDs are potentially useful in biological labeling of cells at a nanometer scale.

Cell Line, Tumor↗

Iridoids from Neopicrorhiza scrophulariiflora and their hepatoprotective activities in vitro.

Four new non-glycosidic iridoids, piscrocins D (1), E (2), F (6), and G (7), as well as two new iridoid glycosides, piscrosides A (8) and B (9), were isolated from the roots of Neopicrorhiza scrophulariiflora (Scrophulariaceae), together with seven known iridoids. The structures of the isolated compounds were established by means of 1D and 2D NMR spectroscopy and chemical methods. The hepatoprotective activities of these compounds were evaluated by measuring their effects on CCl(4)-induced hepatocytes damage in vitro, and the structure-activity relationships were also discussed.

Animals↗

Impaired exercise-induced blood volume in type 2 diabetes with or without peripheral arterial disease measured by continuous-wave near-infrared spectroscopy.

OBJECTIVE: Diabetes is a significant risk factor for peripheral arterial disease (PAD) and is associated with accelerated atherosclerosis and limb loss. However, the pathophysiology involved in PAD is unclear. This study was conducted to evaluate the hemodynamic response to exercise of patients with and without diabetes and PAD. RESEARCH DESIGN AND METHODS: The hemodynamic response in calf muscles of patients with diabetes, PAD, or both was determined using near-infrared spectroscopy (NIRS). Patients performed both a plantar-flexion and treadmill-walking exercise regimen. RESULTS: Skeletal muscle capillary blood volume expansion during exercise, as measured by NIRS, was significantly impaired in the lower extremities of diabetic patients with a normal ankle-brachial index. The relative deoxygenation and oxygenation recovery times measured by NIRS correlates significantly with the presence of PAD. CONCLUSIONS: Patients with diabetes have reduced capillary volume expansion even without PAD. This is likely due to impaired vasodilation secondary to endothelial dysfunction. Further studies are needed to determine whether pharmaceutical intervention improves the blood volume expansion in the diabetic state.

Aged↗

Isolation and characterization of circulating tumor cells in patients with metastatic colorectal cancer.

PURPOSE: Development of targeted therapeutic agents in colorectal cancer (CRC) is impeded by the lack of a noninvasive surrogate of drug effect. This pilot study evaluated the ability of immunomagnetic separation to isolate circulating tumor cells (CTCs) and of the fluorescent microscope system and flow cytometry to enumerate and characterize CTCs from patients with metastatic CRC. PATIENTS AND METHODS: Fifty patients with metastatic CRC contributed 50 mL of blood at treatment initiation and disease evaluation timepoints. Fresh tumor specimens were obtained from 17 patients for comparison of circulating and in situ tumor cell characteristics. Epithelial cells were magnetically isolated from whole blood targeting the antiepithelial cell adhesion molecule (EpCAM). Circulating tumor cells were defined as EpCAM isolated, cytokeratin positive, nuclear stain positive, and CD45 negative. Total RNA was isolated from EpCAM-enriched CTCs and multigene reverse-transcriptase polymerase chain reaction analyses were performed. RESULTS: The median number of CTCs detected by flow cytometry was 2/7.5 mL blood. Mean change in cell count was significantly different for patients with tumor progression versus nonprogression (+6.7 vs. +0.2/7.5 mL; P = 0.001). A correlation was noted between mean fluorescence intensity (flow cytometry) of cytokeratin in CTC and matched tumor specimens (r = 0.79, P = 0.06). Nearly 80% (15 of 19) of samples with >or= 2 CTCs expressed >or= 1 epithelial marker gene (CK19, CK20, carcinoembryonic antigen, or epidermal growth factor receptor). CONCLUSION: Isolating and characterizing CTCs from patients with metastatic CRC is feasible. Change in the CTC number might reflect clinical status, and flow cytometric and gene expression data suggest similarity of circulating and in situ tumor cells. Further evaluation of CTCs for pharmacodynamic and clinical monitoring in patients with CRC is warranted.

Adult↗

[Correlation between integrin subunits alpha5 and beta1 expressions in prostate cancer and its clinical implication].

OBJECTIVE: To explore the correlation between the expression of integrin subunits alpha5 and beta1 in prostate cancer (PCa) and its clinicopathological data including tumor grade and clinical stage. METHODS: Expressions of integrin subunits alpha5 and beta1 were examined in 30 cases of PCa and 30 cases of normal prostatic tissues by immunohistochemical assay. RESULTS: Expressions of integrin subunits alpha5 and beta1 in PCa were lower than those in normal prostatic tissues (P <0.05) respectively. CONCLUSION: Compared with normal prostatic tissues, expressions of integrin subunits alpha5 and beta1 in PCa were rather weaker or even faded. Expressions of integrin subunits alpha5 and beta1 revealed an positive correlation with tumor's Gleason grade and negative with clinical TNM stage. The results indicate that integrin subunits alpha5 and beta1 have potential values in the diagnosis and are predictable indices in the proliferation of PCa.

Aged↗

[Effects of high-volume continuous hemofiltration on inflammatory reaction in experimental porcine pancreatitis in pig].

OBJECTIVE: To investigate the effect of high-volume continuous hemofiltration on inflammatory reaction in experimental severe acute pancreatitis (SAP) in pigs. METHODS: SAP was reproduced in pigs by intraductal injection of sodium taurocholate and trypsin, and they were randomly divided into three groups. Control group consisted of animals with SAP running its spontaneous course. Low-volume continuous venovenous hemofiltration (CVVH) group animals received a low volume (20 ml.kg(-1).h(-1)) CVVH, and high-volume CVVH group animals received a high volume (100 ml.kg(-1).h(-1)) CVVH both started at the onset of SAP. Vital signs were monitored. The serum concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-10, and activated nuclear factor-kappaB (NF-kappaB) levels of peripheral blood mononuclear cell were determined at 0, 6, 12, 24, and 36 hours after the onset of SAP. RESULTS: The median survival time of control, low-volume and high-volume CVVH groups was respectively 41 hours, 50 hours and 65 hours. Survival time of the latter two groups was significantly higher than that in control group (P<0.05 and P<0.01), and the survival time of animals in high-volume CVVH group was significantly higher than low-volume CVVH (P<0.05). In the high-volume CVVH group, plasma contents of TNF-alpha, IL-6 and IL-10 were lower significantly than in the low-volume CVVH and control groups from the beginning to the end of the experiment. In high-volume CVVH group, the expressions of NF-kappaB activation at 6, 12 and 24 hours were lower than those in the control and low-volume CVVH groups respectively. CONCLUSION: Early CVVH can blunt the excessive inflammatory reaction in experiment porcine pancreatitis in pigs, obviously prolong survival time, and improve prognosis. High-volume CVVH is significantly efficacious compared with low-volume CVVH in these respects.

Animals↗

[Effects of intraoperative hybrid procedures for the treatment of congenital heart disease].

OBJECTIVE: A hybrid operation is a joint procedure involving the interventional cardiologist and the cardiac surgeon concomitantly to optimize surgical management for complex congenital heart disease. We analyzed the feasibility and efficacy of this procedure in 20 patients with congenital heart disease. METHODS: Data from 20 patients who underwent intraoperative hybrid procedures from March to October 2005 were analyzed. Two groups were identified: (1) Balloon valvuloplasty group: pulmonary atresia with intact ventricular septum in neonate (n = 3) and severe pulmonary stenosis in infants (n = 4); (2) Device closure group: atrial septum defects (ASD) in child (n = 7), adult ASD (n = 3) and multiple ventricular septum defect (VSD, n = 3). Pulmonary balloon dilation under the guidance of echocardiography together with modified Blalock-Taussig shunt procedure and PDA ligation were applied to patients in balloon valvuloplasty group. For ASD patients, the occluder was placed via right atria after opening the chest either with median sternotomy (4 case) or with submaxillary minimally invasive incision (6 cases), PDA ligation was performed in 1 patient and 2 coronary artery bypass surgeries were performed in 2 adult ASD patients complicating CHD. For multiple VSD, perimembranous VSD was closed surgically and muscular VSD closed by occluder via tricuspid valve approach under cardiopulmonary bypass. RESULTS: All operations were successful and 1 infant received another conventional valvuloplasty due to the pulmonary restenosis after initial balloon valvuloplasty and 1 patient's muscular VSD was closed by conventional procedure after unsuccessful device closure. No device-related complications were found during follow-up (1-6 months). CONCLUSION: Our results showed that intraoperative hybrid procedure was feasible and effective in selected patients with congenital heart disease.

Adolescent↗

[Transcatheter closure of ruptured sinus of valsalva aneurysm using Amplatzer duct occluder].

OBJECTIVE: The present study was conducted to investigate the feasibility and efficacy of transcatheter closure of ruptured sinus of Valsalva aneurysm (RSVA). METHODS: Four patients (3 females) aged 7-57 years with RSVA (3 congenital RSVA and 1 post-surgery RSVA) were involved in the present study. Two-dimensional and color Doppler echocardiography revealed the ruptures of right coronary sinus into right ventricle in all cases. The echo estimated size of the defect was 2-10 mm. After the establishment of the arterio-venous wire loop, Amplatzer Duct Occluder (ADO) was successfully deployed by antegrade venous approach in all patients. The diameter of the occluder was chosen to be at least 1 to 2 mm larger than defect. RESULTS: The defects were successfully occluded without any complications. On the follow-up 3 months after operation, there was no device embolization, infective endocarditis and aortic regurgitation. CONCLUSION: Transcatheter closure is a feasible and effective modality for RSVA without other anomalies.

Adolescent↗

[Effect of HSP72 on acute injury of neonatal cardiomyocytes induced by oxidative stress].

OBJECTIVE: To explore the protective effect of HSP72 on the acute injury of cardiomyocyte induced by oxidative stress. METHODS: Cardiomyocytes of neonatal rats treated with heat shock (42 degrees C, 30 min, recovery for 6 h) to induce the expression of HSP72 and HSP72 antisense oligonucleotide was transformed to block the expression of HSP72. 0.5 mmol/L (final concentration) H2O2 was added into the culture medium to mimic oxidative stress, and to induce the acute injury of neonatal cardiomyocytes. The release of LDH and the total protein synthesis were applied to evaluate the injury of cardiomyocyte of neonatal rats. RESULTS: Oxidative stress could significantly increase the release of LDH, and inhibit the total protein synthesis. By inducing the expression of HSPs, heat shock pretreatment significantly reduced the release of LDH and relieved the oxidative stress-mediated inhibition of total protein synthesis. Moreover, HSP7-2 anti-sense oligonucleotide could remarkably block the protective effect of heat shock pretreatment on the cellular injuries induced by H2O2. CONCLUSION: HSP72 plays a most important role in the acute injury of cardiomyocyte mediated by oxidative stress.

Animals↗

Aortic valve calcium content does not predict aortic valve area.

BACKGROUND AND AIM OF THE STUDY: Aortic stenosis (AS) is a common clinical problem which frequently necessitates aortic valve replacement (AVR). The traditional view of progressive AS is a 1:1 inverse relationship between valve calcium content and aortic valve area (AVA). However, this assumption has been based on subjective estimates of calcification on chest X-radiographic images. The study aim was to evaluate the relationship between AVA as measured with echocardiography compared to calcium quantification using electron beam computed tomography (EBT). METHODS: Sixty-one patients with an AVA between 0.7 and 2.0 cm2 underwent an EBT scan to evaluate the aortic valve calcium content. RESULTS: The mean (+/- SD) aortic valve Agatston calcium score was 1,458.4 +/- 1,362.2, and for the aortic valve volume score was 1,178.8 +/- 1,066.0. The aortic valve Agatston score did not correlate strongly with AVA (r = -0.34, 95% CI -0.54, -0.09; p = 0.007). The data pattern appeared curvilinear, with the poorest correlation noted for those patients with moderate and severe aortic valve calcification. CONCLUSION: The study findings support the hypothesis that the aortic valve orifice area decreases not only due to calcium accumulation but also to sclerotic processes.

Aged↗