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Aims: To compare stent strut coverage using optical coherence tomography (OCT) at three-month follow-up between a PLGA-polymer with electro-grafting base layer sirolimus-eluting stent (SES) (BuMA) and a PLA-polymer SES (EXCEL)., Methods and Results: This prospective, single-centre, non-inferiority randomised BuMA-OCT trial enrolled patients with de novo coronary artery lesions, treated with either the BuMA or the EXCEL stent. The study primary endpoint was OCT-evaluated stent strut coverage at three months. Secondary endpoints were neointimal thickness of stent struts, and incomplete stent apposition evaluated with OCT. A total of 80 patients were randomly assigned to receive the BuMA (n=40) or the EXCEL (n=40) stent. In OCT follow-up (achieved in 86.3% of cases: BuMA, n=33; EXCEL, n=36), the percentage of stent strut coverage was significantly higher in the BuMA vs. the EXCEL group (strut level: 94.2% vs. 90.0%, p<0.01; p(non-inferiority)<0.0001; p(superiority) <0.0001), while the proportion of malapposed struts (strut level: 1.28% vs. 1.80%, p=0.51) and the mean neointimal thickness (strut level: 0.07±0.03 mm vs. 0.06±0.02 mm, p=0.31) were similar. Rates of myocardial infarction (periprocedural non-Q-wave, 7.5% vs. 7.5%, p=1.00) and target lesion failure (7.5% vs. 7.5%, p=1.00) were similar between groups, with no cardiac death or stent thrombosis., Conclusions: In the BuMA-OCT randomised trial, the novel BuMA PLGA-polymer with electro-grafting base layer SES was superior to the EXCEL PLA-polymer SES in the primary endpoint of stent strut coverage at three-month follow-up.

Unlabelled: Viperin is an endoplasmic reticulum (ER)-associated multifunctional protein that regulates virus replication and possesses broad antiviral activity. In many cases, viperin interferes with the trafficking and budding of viral structural proteins by distorting the membrane transportation system. The lentivirus equine infectious anemia virus (EIAV) has been studied extensively. In this study, we examined the restrictive effect of equine viperin (eViperin) on EIAV replication and investigated the possible molecular basis of this restriction to obtain insights into the effect of this cellular factor on retroviruses. We demonstrated that EIAV infection of primary equine monocyte-derived macrophages (eMDMs) upregulated the expression of eViperin. The overexpression of eViperin significantly inhibited the replication of EIAV in eMDMs, and knockdown of eViperin transcription enhanced the replication of EIAV in eMDMs by approximately 45.8%. Further experiments indicated that eViperin restricts EIAV at multiple steps of viral replication. The overexpression of eViperin inhibited EIAV Gag release. Both the α-helix domain and radical S-adenosylmethionine (SAM) domain were required for this activity. However, the essential motifs in SAM were different from those reported for the inhibition of HIV-1 Gag by human viperin. Furthermore, eViperin disrupted the synthesis of both EIAV Env and receptor, which consequently inhibited viral production and entry, respectively, and this disruption was dependent on the eViperin α-helix domain. Using immunofluorescence assays and electron microscopy, we demonstrated that the α-helix domain is responsible for the distortion of the endoplasmic reticulum (ER). Finally, EIAV did not exhibit counteracting eViperin at the protein level., Importance: In previous studies, viperin was indicated as restricting virus replications primarily by the inhibition of virus budding. Here, we show that viperin may have multiple antiviral mechanisms, including the reduction of EIAV Gag budding and Env expression, and these activities are dependent on different viperin domains. We especially demonstrate that the overexpression of viperin inhibits EIAV entry by decreasing the level of virus receptor. Therefore, viperin restriction of viruses is determined largely by the dependence of virus on the cellular membrane transportation system., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

The existence of innate, host-specific restriction factors is a major obstacle to the development of nonhuman primate models for AIDS studies, and TRIM5α is one of the most important of these restriction factors. In recent years, a TRIM5 chimeric gene that was retrotransposed by a cyclophilin A (CypA) cDNA was identified in certain macaque species. The TRIM5α-CypA fusion protein, TRIMCyp, which was expressed in these monkeys, had lost its restriction ability toward HIV-1. We previously found that TRIMe7-CypA, an alternative splicing isoform of the TRIMCyp transcripts, was expressed in pig-tailed and rhesus macaques but absent in long-tailed macaques. In this study, the anti-HIV-1 activity of TRIMe7-CypA in the rhesus macaque (RhTRIMe7-CypA) was investigated. The over-expression of RhTRIMe7-CypA in CrFK, HeLa and HEK293T cells did not restrict the infection or replication of an HIV-1-GFP reporter virus in these cells. As a positive control, rhesus (rh)TRIM5α strongly inhibited the reporter virus. Intriguingly, the anti-HIV-1 activity of RhTRIM5α was significantly reduced in a dose-dependent manner by the co-repression of RhTRIMe7-CypA. Our data indicate that although the RhTRIMe7-CypA isoform does not appear to restrict HIV-1, it may act as a negative modulator of TRIM family proteins, presumably by competitive inhibition., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background and Aims: Epicotyl dormancy break in seeds that have deep simple epicotyl morphophysiological dormancy (MPD) requires radicle emergence and even a certain root length in some species. However, the mechanisms by which root length affects epicotyl dormancy break are not clear at present. This study aims to explore the relationship between root length and epicotyl dormancy release in radicle-emerged seeds of Tibetan peony, Paeonia ludlowii, with discussion of the possible mechanisms., Methods: Radicle-emerged seeds (radicle length 1.5, 3.0, 4.5 and 6.0 cm) were incubated at 5, 10 and 15 °C. During the stratification, some seeds were transferred to 15 °C and monitored for epicotyl-plumule growth. Hormone content was determined by ELISA, and the role of hormones in epicotyl dormancy release was tested by exogenous hormone and embryo culture., Key Results: Cold stratification did not break the epicotyl dormancy until the root length was ≥6 cm. The indole-3-actic acid (IAA) and GA3 contents of seeds having 6 cm roots were significantly higher than those of seeds with other root lengths, but the abscisic acid (ABA) content was lowest among radicle-emerged seeds. GA3 (400 mg L(-1)) could break epicotyl dormancy of all radicle-emerged seeds, while IAA (200 mg L(-1)) had little or no effect. When grown on MS medium, radicles of naked embryos grew and cotyledons turned green, but epicotyls did not elongate. Naked embryos developed into seedlings on a mixed medium of MS + 100 mg L(-1) GA3., Conclusions: A root length of ≥6.0 cm is necessary for epicotyl dormancy release by cold stratification. The underlying reason for root length affecting epicotyl dormancy release is a difference in the GA3/ABA ratio in the epicotyl within radicle-emerged seeds, which is mainly as a result of a difference in ABA accumulation before cold stratification.

Background: Previous studies have suggested that hypothyroidism correlated with coronary heart diseases (CHD) mortality in long-term cohort, but whether the thyroid function status is associated with myocardial injury in acute ST-elevation myocardial infarction (STEMI) has not been investigated sufficiently., Methods: Five hundred and eighty-two hospitalized patients from January 2010 to December 2011, with the diagnosis of STEMI, were enrolled in this study. All patients underwent testing for thyroid function status, cardiac troponin I (cTnI), cardiac enzymes, C-reactive protein (CRP). We investigated the association between thyroid hormone levels and cardiac markers (creatine kinase-MB and cTnI), and thus evaluated the potential role of thyroid function status in predicting the myocardial injury., Results: There were 76 patients (13.06%) who had hypothyroidism including low-T3-syndrome (34 patients, 5.84%), subclinical hypothyroidism (28 patients, 4.81%) and clinical hypothyroidism (14 patients, 2.41%). After adjusting for conventional risk factors (age, gender, smoking, diabetes mellitus, dyslipidemia, hypertension), free triiodothyronine (FT3) was significantly and negatively correlated with log-CKMB (r = -0.244, P < 0.001) and log-cTnI (r = -0.290, P < 0.001), indicating that the lower thyroid hormone level correlates with the severer cardiac injury in STEMI patients. FT3 also had a moderate negative correlation with CRP (r = -0.475, P < 0.001), which might indicate that hypothyroidism may activate the inflammation response. No significant correlation was found between other thyroid parameters (TSH, FT4) and cardiac markers., Conclusions: As the lower FT3 level correlates with higher level of cardiac markers and lower left ventricular ejection fraction (LVEF), the hypothyroidism may be a predictor for myocardial injury in STEMI. And these results may warrant further study to investigate whether reversing the hypothyroidism could benefit the STEMI patients.

Objective: To study the feasibility of the application of ultra high-pressure processing (UHPP) as an anticorrosion and anti-mould method by comparing the total numbers of bacteria and mould colonies and the content of ginsenosides before and after UHPP., Method: The total numbers of bacteria and moulds colony were determined by microbiological test method. The contents of 12 ginsenosides were determined by HPLC., Result: Under the three selected conditions, the total number of bacterial colony decreased significantly, while the mould was not detected in UHPP samples; and the contents of 12 ginsenosides were increased significantly in methanol extracts and water extracts., Conclusion: UHPP not only shows anticorrosion and anti-mould effects, but also enhances the leaching rate of ginsenosides. It is a highly effective, safe and environmental friendly anticorrosion and anti-mould technique for Ranax ginseng worth in-depth study.

The anticoagulation properties of biomaterials are crucial for biomedical applications, especially for blood-contacting materials. In this work, a range of functional graphene oxide based on the biomimetic monomer 2-(methacryloyloxy) ethyl phosphorylcholine (GO-g-pMPC) were synthesized by RATRP in alcoholic media using peroxide groups as initiator, and then filled into the polyurethane matrix to obtain the polyurethane (PU)/functional graphene oxide nanocomposite films (PU/GO-g-pMPC). The tensile strength and elongation and morphology of the PU/GO-g-pMPC were characterized by mechanical properties test, Transmission electron microscope (TEM), respectively. The results showed that a small amount of graphene oxide can improve the mechanical properties of PU. The blood compatibility of the PU substrates was evaluated by protein adsorption tests and platelet adhesion tests in vitro. It was found that all the PU/GO-g-pMPC showed improved resistance to nonspecific protein adsorption and platelet adhesion., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To learn about the prevalence and risk factors of coronary artery disease (CAD) in rheumatoid arthritis (RA)., Methods: Data were obtained from a 12-month retrospective investigation of the patients with RA, randomly selected from Departments of Rheumatology and Immunology in 21 big hospitals in China. The data were collected about their social conditions, clinical conditions, medications associated with RA, such as disease modifying anti-rheumatic drugs (DMARDs), non steroidal anti-inflammatory drugs (NSAIDs), glucocorticoid, biologic agents. A nonparameter test and multivariate logistic regression analysis were performed., Results: In the study, 960 patients were enrolled. The prevalence of CAD was 3.5% in China, which was obviously higher than that of normal people. The prevalence of overweight and obesity, smoking, hypertension, diabetes mellitus, hypercholesterolemia and cerebrovascular disease were 35.1%, 12.3%, 17.0%, 7.7%, 0.4% and 3.0%, respectively. Compared with the control group, the CAD group had higher age [(64.7±9.3) years vs. (52.3±14.0) years,P<0.001], more rheumatoid nodules (14.7% vs. 3.1%,P=0.005), lower rate of hydroxychloroquine (HCQ) use (5.9% vs. 22.6%,P=0.021), higher prevalence rates of lung interstitial disease (17.5% vs. 7.0%,P<0.001), diabetes mellitus and hypertension (29.4% vs. 7.0%,P<0.001; 38.2% vs. 16.2%,P=0.001). There was no obvious correlation of CAD in RA with joint deformity, rheumatoid factor (RF) titer, glucocorticoid use, hypercholesterolemia and body mass index (BMI). Multivariate analysis showed higher age, diabetes mellitus and hypertension were independent predictors of CAD, and the use of HCQ was a protective factor of CAD., Conclusion: The prevalence of CAD is 3.5%. Higher age, diabetes mellitus and hypertension are independent predictors of CAD, and the use of HCQ is a protective factor of CAD.

Myocardial bridging is a common congenital abnormality of a coronary artery, and is usually thought to be a benign anatomical variant. Although rare, previous studies have reported that patients with myocardial bridging may suffer from myocardial ischemia, myocardial infarction (MI), arrhythmias and even sudden death. Here we report the case of an 18-year-old adolescent athlete with myocardial bridging resulting in MI. Coronary angiography revealed 80% luminal narrowing by systolic compression in the proximal and mid segments of the left anterior descending coronary artery, which returned to normal during diastole. We considered that heavy sports might be a potential trigger for his MI attack. Therefore, special attention should be paid to this kind of athlete, especially if adolescent.

Background: Statins are commonly administrated daily, while rosuvastatin can be given every other day due to its longer half-lives. We evaluated the potential efficacy of alternate-day dosing of 10mg rosuvastatin compared with daily dosing of 10mg rosuvastatin with regarding to lipid and inflammatory markers in patients with dyslipidemia., Methods: Thirty-seven patients were randomly divided into the 2 groups: alternate-day group (rosuvastatin 10mg every other day, n=19) and once-daily group (rosuvastatin 10mg every day, n=18) for 6 weeks. The primary endpoints of the study were changes of the serum concentrations of low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP) and interleukin-6 (IL-6) following 6-week rosuvastatin therapy., Results: Baseline characteristics of the 2 groups were well balanced. LDL-C decreased by 37.5% after the once-daily dosing period and by 36.9% after alternate-day dosing period (p>0.05). Both dosing regimens provided similar improvement in high-density lipoprotein cholesterol and triglyceride. And also, both dosing regimens significantly decreased serum concentrations of CRP, which had an 18.3% reduction in once-daily dosing and a 16.7% reduction in alternate-day dosing of rosuvastatin (p>0.05). Moreover, the pattern of plasma IL-6 concentrations was also similar between the two groups (p>0.05)., Conclusions: Alternate-day dosing of rosuvastatin could be effective comparable with once-daily dosing of rosuvastatin in Chinese patients in improving not only lipid profile but also inflammatory markers, which may provide some cost savings and increase the compliance of patients., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The functional significance of the proteasome activator REGγ in the regulation of cell proliferation and apoptosis has been recognized. However, pathological contributions to tumor development remain to be elucidated. Both oncogenic proteins and tumor suppressors are targeted by REGγ for proteasomal degradation. It has been proposed that the role of the REGγ in the pathogenesis of cancer is cell- and context-specific. In this study, we aimed to explore the potential involvement of REGγ in laryngeal carcinomas, comparing protein expression in tumor and adjacent tissues by immunohistochemical staining and Western blot analysis. We also characterized the correlation between the expression of REGγ and the previously identified substrates p53 and p21. We showed that REGγ was abnormally highly expressed in cancer tissues. Statistical analysis revealed that there was a positive relationship between the level of REGγ and the expression of p53 and p21. Our study suggests that REγ overexpression can facilitate the growth of laryngeal cancer cells.

Objective: Atrial septal defect (ASD) is a general term used to describe an opening in the atrial septum that divides the two atria; unless the hole is occluded, it can give rise to serious complications. Given the need for percutaneous deployment for ASD or patent foramen ovale (PFO) occluders, all currently available devices are made of metals (specifically nitinol) and synthetic fabric. However, their permanent presence in the human body is not desirable due to the risks of long-term allergy, toxicity, and complications such as thrombus formation, device arm fracture, and nickel allergy. Once the hole is covered by a newly regenerated tissue, the device is no longer needed; thus it is ideal if the device is fully absorbed by the body when healing is completed., Methods: The "Chinese Lantern" device is made of fully biodegradable polymers featured with a unique pull-fold mechanism. The device was inserted across the ASD/PFO model created on Yorkshire swines through a short sheath by hybrid open surgery. X-ray imaging, echocardiography, and postmortem histopathology were obtained during the 1-month follow-up study period., Results: X-ray imaging showed that the devices were in satisfactory position and stable. Echocardiography showed that there is no shunting from the right atrium to the left atrium, indicating excellent sealing. The in vitro degradation study and postmortem explantation study confirmed that the devices have good integrity during the 1-month trial. Furthermore, the devices appeared to be completely endothelialized after 1 month., Conclusions: This work proves the feasibility of interventional closure of ASD or PFO with an innovative biodegradable device, which we call the "Chinese Lantern" for its symbolic design.

Background: Widespread death of implanted cells hampers the development of stem cell therapy for acute myocardial infarction (AMI). Our previous studies indicated that statins can protect implanted mesenchymal stem cells (MSCs) against the post-infarct microenvironment, thus increasing the therapeutic effect. However, the underlying mechanisms are unclear. The JAK-STAT pathway participates in regulation of stress responses of the myocardium to various insults. This study aimed to detect whether rosuvastatin (ROSU) facilitates the survival, engraftment, and differentiation of allogeneic bone marrow-derived MSCs in the post-infarct heart via the JAK-STAT signaling pathway., Methods and Results: Female Sprague-Dawley rats were randomized into 5 groups: AMI (control), ROSU gavage (group R), MSCs transplantation (group M), MSCs and ROSU (group M+R), or MSCs, ROSU and a JAK2 inhibitor AG-490 (group M+R+AG). MSCs from male rats were injected into the myocardium 1 week after AMI. Cardiac function and histology, as well as the expression of Y-chromosomal genes and JAK-STAT signaling proteins, were examined at 4 weeks after transplantation. Better functional recovery, increased survival and differentiation of MSCs occurred in group M+R. Furthermore, phosphorylation of JAK2 and STAT3 was higher in group M+R. The effects of ROSU, as well as of activated JAK-STAT proteins, could be attenuated by AG-490., Conclusions: ROSU treatment improves the efficacy of stem cell transplantation in infarcted hearts by activation of the JAK2-STAT3 signaling pathway.

Current percutaneous devices for septal defect treatment are made of nondegradable metallic and synthetic fabric materials. These devices are not ideal due to risks of future complications from device erosions and potential obstructed access for future transseptal procedures. The biodegradable double umbrella device was made of fully biodegradable polymers, featured with two discs connected with a stretchable stem. The devices were inserted across the PFO model created on Yorkshire swines through a short sheath by open thoracotomy. Fluoroscopic imaging and echocardiography obtained during the 1-month follow-up study period showed that the devices were in stable position with no shunt. The in-vitro degradation study and post-mortem explantation confirmed that the devices have good integrity and mechanical strength during the 1-month trial. Furthermore, the devices appeared to be well endothelialized after 1 month. These results showed clearly that it is feasible to replace the current nondegradable devices with the new generation biodegradable PFO occluders. This work studied and proved the feasibility of interventional closure of patent foramen ovale (PFO) with a fully biodegradable device, that we call the "double umbrella" (DU) for its symbolic design. © 2010 Wiley-Liss, Inc.

In the title compound, C(16)H(22)Cl(4)N(2)O(2)S, the two imide groups adopt a trans arrangement relative to the central thienyl ring, so the four terminal 2-chloro-ethyl arms adopt different orientations. In the crystal, mol-ecules are linked by weak C-H⋯Cl and C-H⋯O hydrogen bonds into a three-dimensional network.

Background: Post-exercise heart rate recovery (HRR) is an index of parasympathetic function associated with clinical outcomes in populations with and without documented coronary heart disease. Decreased parasympathetic activity is thought to be associated with disease progression in chronic heart failure (HF), but an independent association between post-exercise HRR and clinical outcomes among such patients has not been established., Methods and Results: We measured HRR (calculated as the difference between heart rate at peak exercise and after 1 minute of recovery) in 202 HF subjects and recorded 17 mortality and 15 urgent transplantation outcome events over 624 days of follow-up. Reduced post-exercise HRR was independently associated with increased event risk after adjusting for other exercise-derived variables (peak oxygen uptake and change in minute ventilation per change in carbon dioxide production slope), for the Heart Failure Survival Score (adjusted HR 1.09 for 1 beat/min reduction, 95% CI 1.05-1.13, P < .0001), and the Seattle Heart Failure Model score (adjusted HR 1.08 for one beat/min reduction, 95% CI 1.05-1.12, P < .0001). Subjects in the lowest risk tertile based on post-exercise HRR (>or=30 beats/min) had low risk of events irrespective of the risk predicted by the survival scores. In a subgroup of 15 subjects, reduced post-exercise HRR was associated with increased serum markers of inflammation (interleukin-6, r = 0.58, P = .024; high-sensitivity C-reactive protein, r = 0.66, P = .007)., Conclusions: Post-exercise HRR predicts mortality risk in patients with HF and provides prognostic information independent of previously described survival models. Pathophysiologic links between autonomic function and inflammation may be mediators of this association.

Background: Erythropoietin mitigates myocardial damage and improves ventricular performance after experimental ischemic injury. This study assessed safety and efficacy markers relevant to the biological activity of recombinant human erythropoietin (rHuEpo) in patients with acute myocardial infarction (MI)., Methods: We conducted a prospective, placebo-controlled, randomized, double-blind trial to determine the effects of intravenous rHuEpo (200 U/kg daily for 3 consecutive days) on measures of platelet and endothelial cell activation, soluble Fas ligand, and peripheral blood mononuclear cell (PBMC) expression of angiogenesis signaling proteins in 44 subjects with acute MI treated with aspirin and clopidogrel after successful percutaneous coronary intervention., Results: Recombinant human erythropoietin did not alter bleeding time, platelet function assay closure time, von Willebrand factor levels, soluble P-selectin, or soluble Fas ligand levels when compared with placebo. By contrast, rHuEpo significantly increased expression of erythropoietin receptor, vascular endothelial growth factor receptor Flt-1, and phosphorylated phosphatidylinositol 3-kinase in PBMCs when compared with placebo (all Ps < .05)., Conclusions: In acute MI patients treated with aspirin and clopidogrel, short-term administration of rHuEpo did not alter markers of platelet and endothelial cell activation associated with thrombosis, yet did increase expression of angiogenesis signaling proteins in PBMCs when compared with placebo. These data provide preliminary evidence of safety and biologic activity of rHuEpo at this dosing and support continued enrollment in ongoing efficacy trials.

Drug eluting stents (DES) have become a common mode of treatment for stenosis in coronary arteries. However, currently, the use of sirolimus/paclitaxel-coated DES has come under scrutiny, because of their pro-thrombotic effects leading to potential adverse outcomes in the long run. We have previously documented that D: -threo-1-phenyl-2-decanoylamino-3-morholino propanol (D-PDMP); an inhibitor of glucosylceramide synthase and lactosylceramide (LacCer) synthase markedly inhibited platelet-derived growth factor (PDGF)-induced cell proliferation. We have fabricated DES wherein, D-PDMP or sirolimus was coated on to a double layer of poly (lactic-co-glycolic acid) on a bare metal stent. The in vitro release of D-PDMP from biopolymer and its consequent effect on PDGF induced proliferation and apoptosis was assessed in human aortic smooth muscle cells (ASMC). D-PDMP was released from biopolymers in a dose-dependent fashion and was accompanied with a decrease in PDGF-induced cell proliferation, but not apoptosis. In contrast, sirolimus markedly increased apoptosis in these cells in addition to inhibiting proliferation. Our mechanistic studies revealed that D-PDMP, but not sirolimus decreased the cellular level of glucosyl and lactosylceramide that accompanied inhibition of PDGF-induced cell proliferation. Our short-term (14 days) in vivo studies in rabbits also attested to the safety and biocompatibility of the D-PDMP coated stents. Our data reveal the superiority of D-PDMP coated biopolymers over sirolimus coated biopolymers in mitigating ASMC proliferation. Such D-PDMP coated stents may be useful for localized delivery of drug to mitigate neo-vascular hyperplasia and other proliferative disorders.

Background: ST-elevated acute myocardial infarction (STEAMI) happening in the first month post percutaneous coronary intervention (PCI) is almost related to acute thrombosis or subacute thrombosis in-stents. This study aimed to investigate the possible causes of myocardial infarction one month later., Methods: Patients who had a history of successful PCI, and received coronary angiography or re-PCI due to STEAMI were included in this study. The AMI-related lesions and previous angiographic findings such as the number of lesions, the degree of the stenosis, the type of stents and acute results of last PCI were recorded. If the AMI-related lesion was localized in-stents or at the edge of stents (distance apart from the edge < or = 5 mm), it was defined to be late thrombosis; otherwise as a new-lesion induced AMI., Results: One hundred and ninety-two patients aged 40 - 79 years were included in this study. New lesions, as the cause of STEAMI, were found in 144 patients (Group A, 75%), and late thrombosis in 48 patients (Group B, 25%). Almost all newly built thromboses were found at the sites of previous insignificant lesions (diameter stenosis < 50%). There was a significant difference in the average time from previous PCI to AMI ((30.1 +/- 12.4) vs (20.3 +/- 11.9) months) between the two groups. Diabetes mellitus (DM) and drug-eluting stent (DES) utilization were associated with markedly higher morbidity of late thrombosis in adjusted Logistic regression (hazard ratio (HR) 3.4, 95% confidence interval (CI) 1.1 - 10.9 and 5.3, 95% CI 1.1 - 26.5)., Conclusions: STEAMIs happening 1 month after PCI are more likely to develop from previous insignificant lesion rupture than from late thrombosis in-stents. Moreover, DM and DES are associated with the high incidence of late thrombosis, which may indicate that intensive antiplatelet therapy should be considered in patients with diabetes.

This review article summarizes the current medical literature reporting on the prevalence and prognostic significance of anemia in patients with heart failure. Almost all currently available data indicate that anemia is common in heart failure populations, with the majority of studies indicating prevalence >20%. Anemia appears to be more highly prevalent in patients with advanced age, with more severe limitations in functional capacity, and with greater severity of co-morbid chronic kidney disease. In most reported studies anemia is an independent predictor of increased mortality risk and increased risk of hospitalization for heart failure. These data provide the rationale for interventional treatment trials to determine if anemia is in the causal pathway for disease progression and increased mortality risk in HF patients.

1. The olfactory system can detect the presence of low concentrations of odourant molecules and discriminate even slight differences among molecules with a very similar chemical structure. The detection and discrimination of odourants are correlated with the electrophysiology of the olfactory sensory neurons. To get a better understanding of the molecular mechanisms of olfactory transduction, it is therefore of considerable importance to obtain electrophysiological recordings of olfactory sensory neurons. FMRFamide (Phe-Met-Arg-Phe-NH(2)), secreted from the nerve terminals of the nasal cavity, has been suggested to act as a neurotransmitter or neuromodulator, playing an important role in modulating the activity of olfactory receptor neurons. Its effects on voltage-dependent potassium currents in the mouse olfactory sensory neurons were investigated in the present study using the whole-cell patch-clamp technique. 2. Olfactory sensory neurons were isolated from the Kunming Mouse (KM) mouse olfactory epithelium. Different protocols were applied to obtain delayed-rectifier potassium current (I(K)) and fast transient potassium current (I(A)). The effects of FMRFamide on the outward potassium currents, including I(K) and I(A), in mouse olfactory sensory neurons were investigated. 3. We found that FMRFamide (5 micromol/L) increased the magnitude of I(K). However no effect on I(A) was observed. The activation dynamics of both currents were not changed by FMRFamide. 4. In conclusion, FMRFamide may play a role in the modulation of peripheral olfactory signals by regulating I(K). This modulation may shorten the phase of the fast repolarization of the action potential in mouse olfactory sensory neurons and increase the excitability of the neuronal membrane.

Objective: To explore the infarct sites in patients with inferior wall acute myocardial infarction (AMI) concomitant with ST segment elevation in leads V1-V3 and leads V3R-V5R., Methods: Five patients diagnosed as inferior, right ventricular, and anteroseptal walls AMI at admission were enrolled. Electrocardiographic data and results of isotope 99mTc-methoxyisobutylisonitrile (MIBI) myocardial perfusion imaging and coronary angiography (CAG) were analyzed., Results: Electrocardiogram showed that ST segment significantly elevated in standard leads II, III, aVF, and leads V1-V3, V3R-V5R in all five patients. The magnitude of ST segment elevation was maximal in lead V1 and decreased gradually from lead V1 to V3 and from lead V1 to V3R-V5R. There was isotope 99mTc-MIBI myocardial perfusion imaging defect in inferior and basal inferior-septal walls. CAG showed that right coronary artery was infarct-related artery., Conclusions: The diagnostic criteria for basal inferior-septal wall AMI can be formulated as follows: (1) ST segment elevates > or = 2 mm in lead V1 in the clinical setting of inferior wall AMI; (2) the magnitude of ST segment elevation is the tallest in lead V1 and decreases gradually from lead V1 to V3 and from lead V1 to V3R-V5R. With two conditions above, the basal inferior-septal wall AMI should be diagnosed.

Background: Recombinant human erythropoietin (rHuEpo) reduces myocardial injury in experimental ischemia and has been proposed as a cardioprotective agent for potential use in acute coronary syndromes. Its safety profile in clinical acute ischemic settings is uncertain because rHuEpo has been reported to increase platelet reactivity and the risk of thromboembolism in some disease populations. Whether prothrombotic effects of rHuEpo mitigate the effects of antiplatelet agents used in acute coronary syndrome patients is unknown., Methods: Recombinant human erythropoietin 100, 200, 400 U/kg, or placebo was given intravenously once daily for 3 consecutive days in a double-blind randomized trial in 96 healthy subjects. A single oral dose of aspirin 325 mg or clopidogrel 300 mg was given immediately after the last dose of study drug. Bleeding time and in vitro high shear stress platelet function assays (PFA)-100 were determined before; 5 hours; and 1, 5, and 7 days after aspirin or clopidogrel., Results: Recombinant human erythropoietin at doses of 100 and 200 U/kg did not alter bleeding time or PFA-100 closure times at any time point when compared with placebo. Recombinant human erythropoietin at a dose of 400 U/kg significantly blunted the post-aspirin increase in bleeding time when compared with placebo (P = .03) but did not alter post-clopidogrel bleeding times nor PFA closure times. The 400-U/kg dose did not change hematocrit but did significantly increase the platelet count at 5 days after study drug administration when compared with placebo (P = .014)., Conclusion: Short-term rHuEpo at doses up to 200 U/kg did not mitigate the effects of administration of aspirin or clopidogrel on either in vivo or in vitro measures of platelet function in healthy subjects. The 400-U/kg dose attenuated the effects of aspirin on bleeding time and increased the platelet count. Studies of the effects of rHuEpo on platelet function in patients with coronary artery disease are warranted to further characterize dose/safety profile.

Endothelin 1 is a vasoconstrictive peptide with many biological functions. To investigate the distribution of endothelin 1 in guinea pig cochlear lateral wall and the significance of endothelin 1 in maintaining cochlear homeostasis, the immunohistochemistry avidin biotin complex method was applied by using rabbit anti-endothelin 1 polyclonal antibody as primary antibody. Endothelin-1-like activities were detected in the marginal cells, spiral prominence epithelial cells, outer sulcus cells, stria vascularis capillaries, basal cells and spiral ligament fibrocytes. These results suggest that endothelin 1 may play an important role in maintaining cochlear homeostasis.

Floating dosage forms enable the sustained delivery of drugs in the gastro-intestinal tract. In this study, a type of multi-unit floating gel bead was synthesized with calcium alginate, sunflower oil, and a drug of interest through an emulsification/gelation process. The alginate beads with oil addition were able to continuously float over the medium for 24h under constant agitation while the non-oily beads could not. Three kinds of drugs with different hydrophilicities, ibuprofen, niacinamide and metoclopramide HCl, were tested in the study. The hydrophobic drug ibuprofen was released in a sustained manner for 24h, due to the oil partitioning. With suitable modification, the beads were able to also release the hydrophilic drugs, niacinamide and metoclopramide HCl, for a similar duration. Therefore a floating dosage form that is able to sustain release both hydrophobic and hydrophilic drugs within its extended gastric retention time has been developed.

Four isolates of infectious bursal disease virus (IBDV), isolated from chicken, duck, goose and sparrow in Jiangsu province of China in 2002, were compared. The viruses were stable to the treatments of 60 degrees C for 1 h, pH 2.0 and lipid solvents. Their antigenic relatedness values (R) were from 0.76 to 0.78. Chickens infected with the chicken isolate showed severe clinical symptoms of IBD and the mortality rate was 33.3% (2/6). Chickens infected with the other three viruses survived but their bursas were damaged and the bursa/body-weight ratios were lower than those of the uninfected control (p< 0.01). The titers of anti-IBDV antibody in infected chicken sera reached up to 1600 by virus neutralization and 6400 by ELISA at 10 days post infection. The sequences of the variable region of VP2 were aligned and compared, showing nucleotide variations ranging from 1.5 to 6.7% and deduced aminoacid variations from 0.8 to 2.2%. All had the same heptapeptide, S-W-S-A-S-G-S, Asp279, and Ala284. The four viruses clustered on a phylogenetic tree and were distant from the STC strain. These findings suggested that different bird species naturally infected with IBDV could serve as carriers or reservoirs in IBDV transmission and might play a role in the emergence of variant IBDV.

Growing evidence suggests that thyroid dysfunction may contribute to progression of cardiac disease to heart failure. We investigated the effects of a therapeutic dose of thyroid hormones (TH) on cardiomyopathic (CM) hamsters from 4 to 6 mo of age. CM hamsters had subclinical hypothyroidism (normal thyroxine, elevated TSH). Left ventricular (LV) function was determined by echocardiography and hemodynamics. Whole tissue pathology and isolated myocyte size and number were assessed. TH treatment prevented the decline in heart rate and rate of LV pressure increase and improved LV ejection fraction. The percentage of fibrosis/necrosis in untreated 4-mo-old CM (4CM; 15.5 +/- 2.2%) and 6-mo-old CM (6CM; 21.5 +/- 2.4%) hamsters was pronounced and was reversed in treated CM (TCM; 11.9 +/- 0.9%) hamsters. Total ventricular myocyte number was the same between 4- and 6-mo-old controls but was reduced by 30% in 4CM and 43% in 6CM hamsters. TH treatment completely prevented further loss of myocytes in TCM hamsters. Compared with age-matched controls, resting and maximum coronary blood flow was impaired in 4CM and 6CM hamsters. Blood flow was completely normalized by TH treatment. We conclude that TH treatment of CM hamsters with subclinical hypothyroidism normalized impaired coronary blood flow, which prevented the decline in LV function and loss of myocytes.

Objective: To conduct a study on the methods for establishing a cytological model of mechanical dissociation and culture of spiral ganglion neurons (SGNs) in postnatal mice., Methods: The spiral ganglion neurons were taken from 1-6-day old mice for primary culture. The morphology and the process of axon were observed by use of an inverted/phase contrast microscope. Immunocytochemical identification was performed using fluorescent microscopy., Results: In the state of primary culture in vitro, the SGNs were found to have good cell morphology and axon regeneration power, the surviving cells of SGN(5-7 d) amounted to (78.10 +/- 4.33)/cm2 and the survival period was 7-14 d., Conclusion: We successfully established the methods of mechanical dissociation and culture of SGN cytological model; the cell amount and survival period of SGNs were able to meet the requirement of cytological experiments.

Objective: To investigate the expression of gamma-aminobutyric acid (GABA)A receptor alpha 2 subunit mRNA on rat cochlear spiral neurons and its' significance., Methods: In the rat cochlear paraffin slides, the GABAA alpha 2 receptor in spiral ganglion neuron was detected with in situ hybridization. Digoxigenin-GABAA alpha 2 cDNA probe (549 base pair), anti-digoxigenin-AP(Fab fragments) and BM purple substrate(precipitating) were used., Results: Positive signals(GABAA alpha 2 mRNA) were seen in all cochlear spiral neurons and their nerves. GABAA alpha 2 mRNA was not found in other structure such as bony spiral lamina. As a positive control, GABAA alpha 2 mRNA was seen in Purkinje cells, granule cells and their axons in rat's cerebellum. GABAA alpha 2 mRNA was not found in OMP cDNA probe (olfactory membrane estrogen receptor probe) negative control, non-probe negative control and non-anti-digoxingenin control in cochlear spiral neuron and cerebellum., Conclusion: GABAA alpha 2 receptor has been found in type I spiral neurons and their nerves. It strongly indicates that GABA as a nerve transmitter plays an important role in inhibiting the excessive stimulation transmission of the inner hair cells.

It has been verified that losartan has beneficial effects on ventricular remodeling (VRM) after acute myocardial infarction (AMI), but the effects of carvedilol alone or in combination with losartan on this condition have not been defined. The present study used rats to compare the effects of carvedilol and losartan alone and in combination for preventing VRM after AMI. After ligation of the left coronary artery, 100 surviving female Sprague-Dawley rats were randomly assigned to 1 of 4 groups: (1) AMI control (n=25), (2) carvedilol (Car, 1 mg x kg(-1) x day(-1)) (n=25), (3) losartan (Los, 3 mg x kg(-1) x day (-1)) (n=25), and (4) Car (1 mg x kg (-1). day(-1)) + Los (3 mg x kg(-1) x day (-1)) (n=25). A sham-operated group (n=17) was also randomly selected. Drugs were administered by gastric gavage for 4 weeks. After hemodynamic studies, the hearts were fixed and analyzed pathologically. Exclusive of the rats that had died or had an infarct size <35% or >55%, complete data were obtained for 65 rats, comprising AMI control (n=13), Car (n=12), Los (n=13), combination (n=14), and sham (n=13) groups. There were no significant differences in the size of infarct among the 4 AMI groups (45.8 approximately 46.7%, all p>0.05). Compared with the sham group, left ventricular (LV) end-diastolic pressure (LVEDP), volume (LVV), weight (LVW) and septal thickness (STh) were all significantly increased (all p<0.001), whereas +/-dp/dt was significantly decreased (both p<0.001) in the AMI group. In comparison with the AMI group, LVEDP, LVV, LVW and STh were all significantly decreased (LVEDP: 12.7+/-2.3, 9.7+/-2.8, and 8.6+/-3.5 mmHg vs 20.6+/-2.7 mmHg, all p<0.001; LVV: 0.74+/-0.07, 0.76+/-0.07, and 0.70+/-0.09 ml vs 0.86+/-0.05 ml, all p<0.05; LVW: 668.4+/-52.0, 702.6+/-45.4, and 683.9+/-67.7 mg vs 787.3+/-76.7 mg, p<0.05 approximately 0.001; STh: 1.57+/-0.05, 1.48+/-0.07, and 1.46+/-0.07 mm vs 1.71+/-0.04 mm, all p<0.05), whereas +/-dp/dt was significantly increased (all p<0.05) in the Car, Los, and combination groups, with LVEDP decreasing more in both Los and the combination groups than in the Car group alone (p<0.05) and STh decreasing more in the combination group than in the Car group alone (p<0.05). Carvedilol and losartan alone and in combination all prevent VRM after AMI in rats, with almost equivalent effect.

Objective: To compare the effects of carvedilol and metoprolol in preventing from left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats., Methods: Twenty-four hours after ligating left coronary artery, 105 surviving female SD rats were randomly assigned to AMI control, carvedilol 1 mg/(kg.d) and metoprolol 2 mg/(kg.d) groups. Sham-operated rats (n = 16) were selected randomly as non-infarction control. After four weeks of drugs therapy, hemodynamic studies and pathologic analysis were performed. Exclusive of MI size < 35% or > 55%, complete experimental variables were obtained in 46 rats, which were comprised of AMI (n = 11), carvedilol (n = 12), metoprolol (n = 11), and Sham-operated (n = 12) groups., Results: Compared with sham-operated group, left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV) and weight (LVW), were all significantly increased (P < 0.05-0.001), while maximal rate of rise and fall (+/- dp/dt) of LV pressure as well as their corrected values (+/- dp/dt/LVSP) were all significantly decreased (P < 0.01-0.001) in AMI group. In comparison with AMI group, the LVEDP and LVV were all significantly decreased (all P < 0.001), while +/- dp/dt and +/- dp/dt/LVSP were significantly increased (P < 0.05-0.001) in both carvedilol and metoprolol group, with LVW and RVW only decreased in carvedilol group (P < 0.05-0.01)., Conclusions: 1. Carvedilol can effectively attenuate LVRM, and improve hemodynamics and LV function after AMI in rats, 2. Metoprolol has equivalent beneficial effects as carvedilol on hemodynamics, LV dilatation and function, but not LV hypertrophy.