Vegetation feedback causes delayed ecosystem response to East Asian Summer Monsoon Rainfall during the Holocene.

One long-standing issue in the paleoclimate records is whether East Asian Summer Monsoon peaked in the early Holocene or mid-Holocene. Here, combining a set of transient earth system model simulations with proxy records, we propose that, over northern China, monsoon rainfall peaked in the early Holocene, while soil moisture and tree cover peaked in the mid-Holocene. The delayed ecosystem (soil moisture and tree cover) response to rainfall is caused by the vegetation response to winter warming and the subsequent feedback with soil moisture. Our study provides a mechanism for reconciling different evolution behaviors of monsoon proxy records; it sheds light on the driving mechanism of the monsoon evolution and monsoon-ecosystem feedback over northern China, with implications to climate changes in other high climate sensitivity regions over the globe.

Characterization of lithium zinc titanate doped with metal ions as anode materials for lithium ion batteries.

With the aim of improving the ionic and electronic conductivities of Li2ZnTi3O8 for high performance lithium ion battery applications, Li2Zn0.9M0.1Ti3O8 (M = Li+, Cu2+, Al3+, Ti4+, Nb5+, Mo6+) compounds are successfully fabricated using facile high temperature calcination at 800 °C. Physical characterization and lithium ion reversible storage demonstrate that Zn-site substitution by multivalent metal ions is beneficial for improving the migration rate of ions and electrons of Li2ZnTi3O8. X-ray diffraction analysis and scanning electron microscopy reveal that the crystal structure and microscopic morphology of bare Li2ZnTi3O8 do not change by introducing a small amount of foreign metal ions. As a result, Li2Zn0.9Nb0.1Ti3O8 retains a reversible capacity as high as 198 mA h g-1 at the end of the 500th cycle among all samples. Even when cycled at high temperatures, Li2Zn0.9Nb0.1Ti3O8 still maintains excellent reversible discharge capacities of 210 mA h g-1 and 196 mA h g-1 at 1000 mA g-1 for the 100th cycle at 50 °C and 60 °C, respectively. All the conclusions indicate that Li2Zn0.9Nb0.1Ti3O8 is a high-performance anode material for large-scale energy storage devices.

Effects of a High Dose of the Contrast Medium Iodixanol on Renal Function in Patients Following Percutaneous Coronary Intervention.

Iodixanol is associated with lower rates of contrast-induced acute kidney injury (CI-AKI). However, the effects of high volumes of iodixanol on renal function after percutaneous coronary intervention (PCI) have not been fully elucidated. This study evaluates the effects of high-dose (>300 mL) iodixanol on renal function within 72 hours of PCI. We retrospectively reviewed 676 consecutive patients who received high-dose (>300 mL) iodixanol during PCI between October 2015 and December 2017 in 4 centers. Logistic regression analysis was used to identify significant independent predictors for CI-AKI. The incidence of CI-AKI was 3.5% (23/651). In patients administered 300 to 500 mL and >500 mL iodixanol, the incidence of CI-AKI was 3.9% and 1.7%, respectively. In patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, the incidence of CI-AKI was 2.6%. In high-risk and very high-risk patients, stratified by the Mehran risk score, the incidence of CI-AKI was 3.3% and 4.3%, respectively. In patients received high-dose iodixanol (>300 mL), logistic regression analysis demonstrated that female sex, chronic kidney disease, and eGFR were independent risk factors for CI-AKI, but contrast volume was not. The administration of high (300-500 mL) and very high (>500 mL) dose of iodixanol is associated with low rates of CI-AKI.

Association between Low Free Triiodothyronine Levels and Poor Prognosis in Patients with Acute ST-Elevation Myocardial Infarction.

BACKGROUND: Low free triiodothyronine (fT3) levels are generally associated with poor prognosis in patients with heart diseases, but this is controversial and there is a lack of data about ST-elevation myocardial infarction (STEMI) in Chinese patients. OBJECTIVE: To assess the association between fT3 levels and the prognosis of patients with STEMI. METHODS: This was a prospective observational study of 699 consecutive patients with STEMI treated at the Xinqiao Hospital between January 1, 2013, and December 31, 2014. The patients were divided into the low fT3 (fT3 < 3.1 pmol/L; n = 179, 27.5%) and normal fT3 (fT3 ≥ 3.1 pmol/L; n = 473, 72.5%) groups according to fT3 levels at admission. Patients were followed up at 1, 3, 6, and 12 months for all-cause death and major adverse cardiac events (MACE). RESULTS: During the 1-year follow-up, there were 70 all-cause deaths (39.1%) in the low fT3 group and 40 (8.5%) in the normal fT3 group (P < 0.001). MACE occurred in 105 patients (58.7%) in the low fT3 group and 74 (15.6%) in the normal fT3 group (P < 0.001). Multivariate Cox proportional hazards regression analysis indicated that fT3 levels were independently associated with 30-day and 1-year all-cause death [30-day: hazard ratio (HR) = 0.702, 95% confidence interval (95% CI): 0.501-0.983, P = 0.04; 1-year: HR = 0.557, 95% CI: 0.411-0.755, P < 0.001] and MACE (30-day: HR = 0.719, 95% CI: 0.528-0.979, P = 0.036; 1-year: HR = 0.557, 95% CI: 0.445-0.698, P < 0.001). CONCLUSION: Low fT3 levels were strongly associated with poor prognosis in patients with STEMI. Measurement of fT3 levels may be a valuable and simple way to identify high-risk STEMI patients.

A "Jail Escape Technique" (JET) for distal side branch wiring during provisional stenting: Feasibility and first-in-man study.

OBJECTIVE: To evaluate the feasibility of a novel technique for achieving distal SB access and improve strut apposition during provisional stenting. BACKGROUND: While distal rewiring and stent expansion toward the side branch (SB) are associated with better results during provisional stenting of coronary artery bifurcation lesions, these techniques are technically challenging and often leave unopposed struts near the carina. METHODS: The "Jail Escape Technique" (JET) is performed by passing the proximal tip of the SB wire between the main vessel (MV) stent struts and balloon before implantation, allowing the MV stent to push the SB wire against the distal part of the carina. The MV stent can then be deployed without jailing the SB wire. Distal SB access and strut distribution at the carina were tested in phantom and swine models. Stent distortion, dislodgement forces, and material damage were evaluated with tensile testing. Human feasibility was then tested on 32 patients. RESULTS: Preclinical testing demonstrated that the SB wire was located at the most distal part of the carina and no strut malapposition at the carina was present after balloon inflation. Stent distortion, dislodgement forces, or material damage were not affected. JET was successfully performed in 30 of 32 patients. No major adverse cardiovascular events occurred in any patient at 6-month follow-up. CONCLUSION: The "JET" enables distal SB access and eliminates strut malapposition at the carina. Further studies with larger numbers of patients are needed to further investigate this technique.

N-terminal pro-brain natriuretic peptide and cardiovascular or all-cause mortality in the general population: A meta-analysis.

The prognostic role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the general population remains controversial. We conducted this meta-analysis to investigate the association between baseline NT-proBNP concentrations and cardiovascular or all-cause mortality in the general population. PubMed and Embase databases were systematically searched from their inception to August 2016. Prospective observational studies that investigated the association between baseline NT-proBNP concentrations and cardiovascular or all-cause mortality in the general population were eligible. A summary of the hazard ratio (HR) and 95% confidence interval (CI) of mortality were calculated by the highest versus the lowest category of NT-proBNP concentrations. Eleven studies with a total of 25,715 individuals were included. Compared individuals in the highest with those in the lowest category of NT-proBNP, the pooled HR was 2.44 (95% CI 2.11-2.83) for all-cause mortality, 3.77 (95% CI 2.85-5.00) for cardiovascular mortality, and 2.35 (95% CI 1.45-3.82) for coronary heart disease mortality, respectively. Subgroup analyses indicated that the effects of NT-proBNP on the risk of cardiovascular mortality (RR 2.27) and all-cause mortality (RR 3.00) appeared to be slightly lower among men. Elevated NT-proBNP concentrations appeared to be independently associated with increased risk of cardiovascular and all-cause mortality in the general population.

In-stent Anchoring Facilitating Side-branch Balloon Delivery for Final Kissing: A Prospective, Single-center Registry Study.

BACKGROUND: Recrossing the compromised side branch (SB) with a balloon is sometimes technically challenging. The aim of this study was to evaluate whether in-stent anchoring (ISA) is safe and effective to facilitate SB balloon delivery for final kissing. METHODS: One hundred and fifty-nine consecutive patients were included (166 bifurcation lesions) in this prospective, single-center registry. ISA was used as a bailout method after unsuccessful SB crossing using conventional techniques, including low-profile balloons. Technique success was defined as SB balloon delivery and final kissing. RESULTS: Kissing-balloon delivery was successfully performed with conventional strategies in 149 of 166 lesions (89.8%). In the remaining 17 lesions (10.2%), recrossing of the main vessel stent strut was not successful; therefore, ISA was attempted. The balloon successfully crossed the stent struts, and final kissing was achieved in 15 of 17 lesions (88.2%). Total final kissing was achieved in 164 of 166 lesions (98.8%), with success rates of 100% in the single-stent group and 97.6% in the two-stent group. Two cases without balloon delivery had complex bifurcation lesions with severe calcification. There was no vessel dissection in the anchoring zone. CONCLUSIONS: ISA is safe and effective for recrossing stent struts when conventional low-profile balloons have failed. However, large-scale trials are warranted for further evaluation.

vwF A3-GPI modification of EPCs accelerates reendothelialization of injured vessels via collagen targeting in mice.

Despite the potential of endothelial progenitor cells (EPCs) to incorporate into sites of vessel injury and differentiate into endothelial cells, thereby contributing to the improvement of endothelial function, reendothelialization in some patients is insufficient for the prevention of abnormal endothelial growth because there is a lack of specific guided signals and low levels of congregation of the EPCs to the injured areas. If some type of molecular tool was able to guide EPCs specifically to the injured vessels, however, then the efficacy of cell implantation would improve. Here, we designed a strategy to modify these cells and improve their ability to directly target the injured vessels. As a homing molecule, we selected extracellular matrix components, such as collagen, which is exposed on catheter-injured arteries. To promote the adhesion of the EPCs to collagen, we painted the primary EPCs with a recombinant, glycosylphosphatidylinositol (GPI)-linked high-affinity ligand for collagen that is termed von Willebrand factor A3-GPI. These painted EPCs specifically bound to collagen in vitro and traveled to the damaged vessel in vivo. This novel strategy may allow for significant advancements in EPCs transplantation treatment.

Protective effect of a polysaccharide from Salvia miltiorrhiza on isoproterenol (ISO)-induced myocardial injury in rats.

In this study, we investigated the cardioprotective effect of one purified polysaccharide (SMP1) from Salvia miltiorrhiza on isoproterenol (ISO)-induced myocardial infarction (MI) in rats. ISO-treated rats showed severe myocardial damage and high lipid peroxidation level, as well as decreased endogenous myocardial antioxidant function. Pretreatment with SMP1 (100 and 400mg/kg) for 30 days significantly increased the body weight, decreased the heart weight, attenuated the serum levels of creatine kinase (CK), creatine phospokinase-MB (CK-MB), dehydrogenase (LDH), alkaline phosphate (ALP), aspartate transaminase (AST), alanine transaminase (ALT), total cholesterol, triglyceride, and LDL-cholesterol (LDL-C), along with the increased concentration of HDL-cholesterol (HDL-C). In addition, SMP1 also enhanced myocardial superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities and elevated myocardial reduced glutathione (GSH) level, along with a decrease in thiobarbituric acid reactive substances (TBARS) concentration. Collectively, our results indicated that long-term oral administration of SMP1 offered significant protection against the damage induced by ISO in rat heart through enhancement of endogenous antioxidants and antihyperlipidemic activity.

Cardiovascular effects in vitro of a polysaccharide from Salvia miltiorrhiza.

A polysaccharide (SMP1) was isolated from the roots of Salvia miltiorrhiza. This study is designed to investigate whether SMP1 prevents H9c2 cells from hydrogen peroxide (H2O2)-induced apoptosis. The present study showed that exposure of H9c2 cells to 100mM H2O2 for 24h caused a significant increase in cell death and apoptosis, but pretreatment with SMP1 eliminated H2O2-induced apoptotic cell death. Furthermore, pretreatment with SMP1 significantly prevented the mitochondria disruption, cytochrome c release, the rise of the ratio between proapoptotic Bax and antiapoptotic Bcl-2 protein expression, and caspase-3 activation in H9c2 cells upon H2O2 stimulation. Moreover, the decline of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities together with the elevation of malondialdehyde (MDA) in PC12 cells exposed to H2O2 were remarkably reversed to normal levels by pretreatment with SMP1. These results suggest that SMP1 protects H9c2 cells from H2O2-induced apoptosis through inhibition of mitochondrial dysfunction, inactivation of caspase-3 cascade and enhancement of antioxidant capacity.

In-stent anchoring facilitates balloon delivery for final kissing.

Kissing-balloon inflation has been developed for percutaneous bifurcation interventions to improve outcomes and reduced angiographic (re)stenosis. However, this procedure is sometimes technically challenging due to inability to deliver the side-branch (SB) balloon across the structure of the main vessel stent(s). The balloon anchoring technique is reported to enable equipment delivery through complex lesions. However, the most important limitation is injury at the site of balloon inflation. In this paper, we describe an improved in-stent anchoring technique to facilitate balloon delivery to SB and at the same time avoid intimal injury.

Comparison of two molecular scaffolds, 5-methylisoxazole-3-carboxamide and 5-methylisoxazole-4-carboxamide.

Leflunomide is a disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Structurally, it is a derivative of 5-methylisoxazole-4-carboxamide. Upon metabolism, the N-O bond in the isoxazole ring is cleaved to form the active metabolite, teriflunomide, which was recently approved by the FDA for the treatment of multiple sclerosis. Both leflunomide and teriflunomide inhibit dihydroorotate dehydrogenase (DHODH) thereby inhibiingt the synthesis of pyrimidine. For both drugs, the two major concerns are potential liver toxicity and teratogenicity. It was suspected that these undesirable effects might be related to the cleavage of the N-O bond. We herein summarize the metabolites-toxicity issues related to leflunomide/teriflunomide and discuss two related molecular platforms, UTL-4 and UTL-5. UTL-4 compounds are based on the same scaffold of leflunomide; their toxicological and pharmacological effects are not significantly different from those of leflunomide/teriflunomide. In UTL-5 series, the leflunomide scaffold is changed into 5-methylisoxazole-3-carboxamide. Unlike leflunomide, the N-O bond of a UTL-5 compound, UTL-5b, is not cleaved upon metabolism; instead, the peptide bond is cleaved to form its major metabolites. UTL-5b and its metabolites do not inhibit DHODH in vitro. In addition, UTL-5b and all other UTL-5 compounds have lower acute toxicity than leflunomide/teriflunomide. Furthermore, from leflunomide to UTL-5b/UTL-5g, the potential liver toxicity becomes liver protective effect. With the reduced toxicity, UTL-5 compounds still maintain significant pharmacological effects including anti-inflammatory and antiarthritic effects. In summary, our observations provide a valuable direction in drug optimization based on the modification of the leflunomide scaffold.

Baseline serum uric acid level as a predictor of cardiovascular disease related mortality and all-cause mortality: a meta-analysis of prospective studies.

OBJECTIVE: Serum uric acid (SUA) levels have been used to predict cardiovascular and all-cause mortality event, but the data have yielded conflicting results. We investigated whether SUA was an independent predictor for cardiovascular or all-cause mortality with prospective studies by meta-analysis. METHODS: Pubmed and Embase were searched without language restrictions for publications available till April 2013. Only prospective studies on cardiovascular or all-cause mortality related to SUA levels were included. Pooled adjust relative risk (RR) and corresponding 95% confidence intervals (CI) were calculated separately for the highest vs. lowest category or the lowest vs. middle category. RESULTS: For the highest SUA, eleven studies with 172,123 participants were identified and analyzed. Elevated SUA increased risk of all-cause mortality (RR 1.24; 95% CI 1.09-1.42) and cardiovascular mortality (RR 1.37; 95% CI 1.19-1.57). Subgroup analyses showed that elevated SUA significantly increase the risk of all-cause mortality among men (RR 1.23; 95% CI 1.08-1.42), but not in women (RR 1.05; 95% CI 0.79-1.39). Risk of cardiovascular mortality appeared to be more pronounced among women (RR 1.35; 95% CI 1.06-1.72). The association between extremely low SUA and mortality was reported in three studies; we did not perform a pooled analysis because of high degree of heterogeneity in these studies. CONCLUSIONS: Baseline SUA level is an independent predictor for future cardiovascular mortality. Elevated SUA appears to significantly increase the risk of all-cause mortality in men, but not in women. Whether low SUA levels are predictors of mortality is still inconclusive.

Beneficial effects of a polysaccharide from Salvia miltiorrhiza on myocardial ischemia-reperfusion injury in rats.

In the present study, one water-soluble polysaccharide (SMP1) was isolated from the roots of Salvia miltiorrhiza. The cardio-protective potential of SMP1 was studied in the ischemia-reperfusion (I/R) model of rats in vivo. Results showed that 30 min of left anterior descending coronary artery occlusion (LAD) followed by 4 h of reperfusion markedly decreased myocardial superoxide dismutase (SOD), Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities and increased myocardial malondialdehyde (MDA) level and serum activities of creatine kinase (CK) and lactate dehydrogenase (LDH) in I/R rats. An increase in infarct size and high apoptosis index of cardiac cell were also observed in IR rats. Administration of SMP1 400 and 800 mg/kg significantly reversed these biochemical parameters in the I/R rats to the normal levels in sham control rats. The infarct sizes and the percent of TUNEL-positive cells were found significantly decreased in SMP1-treated groups compared to I/R rats. Taken together, the present study clearly suggests SMP1 has a protective effect against myocardial I/R injury in rats by ameliorating oxidative stress and inhibiting myocardial apoptosis.

Evaluation on the efficacy and safety of domestic bivalirudin during percutaneous coronary intervention.

BACKGROUND: Bivalirudin was widely used as an anticoagulant during coronary interventional procedure in western countries. However, it was not available in China before this clinical trial was designed. This randomized, single-blind and multicenter clinical trial aimed to evaluate the efficacy and the safety of domestic bivalirudin during percutaneous coronary intervention (PCI). METHODS: A randomized, single-blind, multicenter trial was designed. Elective PCI candidates in five centers were randomized into a bivalirudin group and a heparin group, which were treated with domestic bivalirudin and non-fractional heparin during the PCI procedure. The efficacy was evaluated by comparing the activated coagulation time (ACT), the procedural success rate (residual stenosis < 20% in target lesions without any coronary artery related adverse events within 24 hours after PCI), and the survival rate without major adverse cardiac events at 30 days after PCI between the two groups. Safety was evaluated by the major/minor bleeding rate. RESULTS: A total of 218 elective PCI patients were randomized into a bivalirudin group (n = 110) and heparin group (n = 108). Except for two patients needing additional dosing in the heparin group, the ACT values of all other patients in both groups were longer than 225 seconds at 5 minutes after the first intravenous bolus. Procedural success rates were respectively 100.0% and 98.2% in the bivalirudin group and heparin group (P > 0.05). Survival rates without major adverse cardiac events at 30 days after PCI were 100.0% in the bivalirudin group and 98.2% in the heparin group (P > 0.05). Mild bleeding rates were 0.9% and 6.9% (P < 0.05) at 24 hours, and 1.9% and 8.8% (P < 0.05) at 30 days after PCI in the bivalirudin group and heparin group respectively. There was one severe gastrointestinal bleeding case in the heparin group. CONCLUSIONS: Domestic bivalirudin is an effective and safe anticoagulant during elective PCI procedures. The efficacy is not inferior to heparin, but the safety is superior to heparin.

Isthmin inhibits glioma growth through antiangiogenesis in vivo.

Among glioma treatment strategies, antiangiogenesis emerges as a meaningful and feasible treatment approach for inducing long-term survival. Isthmin is a gene highly expressed in the isthmus of the midbrain-hindbrain organizer in Xenopus, and has recently been identified as a novel angiogenesis inhibitor. However, the potential of isthmin on the glioma angiogenesis has not been well studied. In the present study, we demonstrated that the recombinant adenovirus isthmin (Ad-isthmin) could inhibit VEGF-stimulated endothelial cell proliferation and induce apoptosis through a caspase-dependent pathway. In addition, Ad-isthmin significantly suppressed glioma growth through antiangiogenesis without apparent side effects. Taken together, our results demonstrated that isthmin could act as a novel angiogenesis inhibitor and might be utilized in the glioma antiangiogenesis therapy.

Clinical outcome and left ventricular remodeling in AMI patients with insufficient myocardial reperfusion after recanalization.

AIM: Myocardial contrast echocardiography (MCE) is effective in predicting myocardial viability and functional recovery on a segmental level in patients with acute myocardial infarction (AMI). In this study, we investigated whether insufficient myocardial reperfusion plays an important role in left ventricular (LV) remodeling and functional recovery in patients with thrombolysis in myocardial infarction (TIMI) flow grade 3 and corrected TIMI frame count (CTFC) < 40 after recanalization of the infarct-related artery. METHOD: Patients underwent intracoronary injection of microbubbles for echocardiographic assessment of myocardial microvascular perfusion, wall motion score, LV volume and ejection function (EF) at baseline, 30 minutes, one month and six months after recanalization. The patients with MCESI < 1 were considered to have insufficient myocardial reperfusion (group A, n=11), while the patients with MCESI≥1 were considered to have sufficient myocardial reperfusion (group B, n=47) after AMI recanalization. RESULTS: The wall motion score index (WMSI) and the left ventricular ejection fraction (LVEF) showed significant improvement at 1 month and 6 months in group B, but only at six months in group A. Left ventricular end-systolic and end-diastolic volumes (LVESV and LVEDV) were also significantly decreased at one and six months in group B. WMSI, LVESV, LVEDV and LVEF were significantly improved in group B in comparison with group A at one month and six months (P < 0.01). By six months, significant correlations were seen in all patients between MCESI and changes in LVESV, LVEDV and LVEF at 6 months. Similar correlations were observed between the myocardial regional blood flow (Q) and changes in LVESV , LVEDV and LVEF. CONCLUSION: Insufficient myocardial reperfusion was a strong independent predictor of LV remodeling and functional recovery in AMI patients with TIMI flow grade 3 and CTFC < 40 after recanalization. MCE has important additional value for prognosis and risk assessment in patients with acute myocardial infarction following recanalization.

Isolation and characterization of human coronary artery-derived endothelial cells in vivo from patients undergoing percutaneous coronary interventions.

BACKGROUND/AIMS: Human coronary artery-derived endothelial cells (ECs) seem to be the most appropriate cells for the pathogenesis study of coronary artery disease. But limited availability of endothelial tissue is a major constraint. In this study, we developed a method to isolate human coronary artery ECs in vivo from patients. METHODS: Coronary guidewires were used to obtain EC samples from coronary arteries in 76 patients. Cells were eluted from wire tips and purified by immunomagnetic beads. Von Willebrand factor and CD31 were used as immunocytochemical markers to identify cells as endothelium. Cell viability was evaluated in terms of cell membrane integrity, energy-dependent uptake of DiI-labeled acetylated low-density lipoprotein, and apoptosis. Nitric oxide synthase (eNOS) expression and nitric oxide (NO) production of cells were detected to evaluate cell function. RESULTS: About 96 coronary artery ECs were obtained per guidewire. Cells manifested endothelial morphology and immunoreactivity for von Willebrand factor and CD31 with good viability. But eNOS expression and NO production of cells were decreased. CONCLUSIONS: Viable coronary endothelium could be obtained during routine percutaneous coronary interventions combined with immunomagnetic beads. These cells may be used for advanced cellular functional analyses such as immunocytochemistry and molecular biology. Such information could aid in understanding mechanisms of coronary artery diseases.

Low osmolar contrast medium induces cellular injury and disruption of calcium homeostasis in rat glomerular endothelial cells in vitro.

The mechanisms of contrast medium (CM)-induced renal impairment at cellular level are not fully understood. The purpose of this study was to investigate the toxic effects of non-ionic low osmolar contrast medium (LOCM) on glomerular endothelial cells (GECs). Ioversol, the most representative LOCM used in clinic, was chosen to act on primary cultured rat GECs. When rat GECs were treated with various amount of ioversol, a dose-dependent reduction in cell viability was observed by tetrazolium dye (MTT) assay. After exposure to ioversol at dose of 100 microl/ml for 24h, nuclear condensation, nuclear fragmentation, cell apoptosis and necrosis were found in GECs. The intracellular free Ca(2+) concentrations ([Ca(2+)]i) detected by confocal laser scanning were markedly elevated in GECs treated with ioversol. The [Ca(2+)]i increase, LDH release and expression changes of apoptotic associated proteins in GECs induced by ioversol could be reversed by pretreatment with intracellular Ca(2+) chelator, 1,2-bis (o-aminophenoxy) ethane-N,N,N',N'-tetra-acetic acid (BAPTA/AM). These results suggest that LOCM can decrease cell viability and cause cell injury of GECs. The elevation of [Ca(2+)]i released from intracellular calcium stores likely contribute to the LOCM-induced cell injury of GECs.

Comparison of collagen versus adenosine diphosphate in detecting antiplatelet effect in patients with coronary artery disease.

Widely varying methods of assessing platelet aggregation have resulted in the absence of an established standard approach to assess the effects of antiplatelet drugs. The objective of this study was to compare the roles of collagen and adenosine diphosphate (ADP) in the assessment of effects of aspirin or clopidogrel on platelet aggregation. Sixty patients with documented coronary artery disease were assigned to receive aspirin alone (ASA 100 mg/d) (n=30) or aspirin-plus-clopidogrel (ASA 100 mg/d+C 75 mg/d) (n=30). Platelet aggregation assessment by the use of whole blood aggregation tests with collagen or ADP was performed in these patients and 30 age- and gender-matched normal volunteers. When compared with the control group, therapy with ASA or ASA+C resulted in significant inhibition of collagen-induced platelet aggregation (P<0.001 for each), but there was no statistically significant difference in the results between the ASA and ASA+C groups. When platelet aggregation was induced by ADP, the combined therapy with aspirin and clopidogrel decreased platelet aggregation significantly when compared with aspirin alone (P<0.001), and no significant difference in the results between the ASA and normal groups was observed. In conclusion, collagen may prove useful to study the effect of aspirin and ADP may be appropriate for assessing the inhibitory effect of clopidogrel.