[Effect of intracoronary autologous bone marrow mononuclear cells transplantation on arrhythmia in canines].

Objective: To observe the survival and the differentiation of grafted bone marrow cells (BM-MNCs) in host myocardium. To observe whether BM-MNCs transplantation can potentially cause arrhythmia and whether the BM-MNCs transplantation can alter the spatial distribution of connexins, important mediator for arrhythmia genesis after myocardial infarction. Methods: Acute myocardial infarction (AMI) was induced by left anterior descending coronary artery (LAD) ligation in hybrid canine. BM-MNCs suspension was prepared by density centrifugation. The BM-MNCs were labeled with CM-DiI. Sixteen hybrid canines were randomly divided into transplantation group and control group. BM-MNCs (transplantation group, n=10) or saline (control group, n=6) were intracoronarily infused into infarction related artery at 2 hours after AMI. At 6 weeks after AMI, ventricular fibrillation (VF) was induced in infarct area and periinfarct area. The effective refractive period (ERP) of different areas in myocardium was assessed and the expression of connexin 43 (Cx43) was assessed by immunohistochemical staining. Results: Six weeks after the BM-MNCs transplantation, CM-DiI labeled BM-MNCs were mainly located within periinfarct and infarct area. Some BM-MNCs were positive for Cx43. Combined" CM-DiI and FITC" in images were observed. VF was induced in 2 out of the 10 canines in transplantation group and in 2 out of the 6 canines in control group in infarct area. VF was not induced in periinfarct area of both groups. The ERP of infarct area ((85.0±9.3) ms vs. (90.0±7.1)ms, P>0.05), periinfarct area (87.8±9.4 vs. 90.0±7.1, P>0.05) and normal area (85.0±12.0 vs. 88.3±9.4, P>0.05) was similar between transplantation group and control group. The expression of Cx43 in normal area was similar between transplantation group and control group (3 543.7±446.0 vs. 3 431.7±421.5, P>0.05). The expression of Cx43 in periinfarct area of transplantation group was significantly higher than that in control group (2 312.5±412.0 vs. 1 356.2±332.7, P<0.05), but was still much less than in normal area (2 312.5±412.0 vs. 3 543.7±446.0, P<0.05). The expression of Cx43 in infarct area was similar between transplantation group and control group (327.0±98.7 vs. 311.3±78.7, P>0.05). Conclusions: The implanted BM-MNCs could survive in the infarcted lesion and differentiate into cells expressing Cx43.In transplanted group, VF was not induced in periinfarct area. ERP of infarct area, periinfarct area and normal area is similar between two groups. The expression of Cx43 in periinfarct area was significantly higher in transplantation group than that in control group.

Haplotype divergence and multiple candidate genes at Rphq2, a partial resistance QTL of barley to Puccinia hordei.

KEY MESSAGE: Rphq2, a minor gene for partial resistance to Puccinia hordei , was physically mapped in a 188 kbp introgression with suppressed recombination between haplotypes of rphq2 and Rphq2 barley cultivars. ABSTRACT: Partial and non-host resistances to rust fungi in barley (Hordeum vulgare) may be based on pathogen-associated molecular pattern (PAMP)-triggered immunity. Understanding partial resistance may help to understand non-host resistance, and vice versa. We constructed two non-gridded BAC libraries from cultivar Vada and line SusPtrit. Vada is immune to non-adapted Puccinia rust fungi, and partially resistant to P. hordei. SusPtrit is susceptible to several non-adapted rust fungi, and has been used for mapping QTLs for non-host and partial resistance. The BAC libraries help to identify genes determining the natural variation for partial and non-host resistances of barley to rust fungi. A major-effect QTL, Rphq2, for partial resistance to P. hordei was mapped in a complete Vada and an incomplete SusPtrit contig. The physical distance between the markers flanking Rphq2 was 195 Kbp in Vada and at least 226 Kbp in SusPtrit. This marker interval was predicted to contain 12 genes in either accession, of which only five genes were in common. The haplotypes represented by Vada and SusPtrit were found in 57 and 43%, respectively, of a 194 barley accessions panel. The lack of homology between the two haplotypes probably explains the suppression of recombination in the Rphq2 area and limit further genetic resolution in fine mapping. The possible candidate genes for Rphq2 encode peroxidases, kinases and a member of seven-in-absentia protein family. This result suggests that Rphq2 does not belong to the NB-LRR gene family and does not resemble any of the partial resistance genes cloned previously.

Unification of catalytic oxygen reduction and hydrogen evolution reactions: highly dispersive Co nanoparticles encapsulated inside Co and nitrogen co-doped carbon.

The Co nanoparticles encapsulated inside Co and nitrogen co-doped carbon catalysts with small particle size and homogenous distribution of Co NPs were elaborately synthesized, which exhibit evidently outstanding activity and stability toward ORR/HER.

Oxymatrine suppresses proliferation and induces apoptosis of hemangioma cells through inhibition of HIF-1a signaling.

Oxymatrine (OMT), a natural quinolizidine alkaloid, has been known to have anti-inflammation, anti-anaphylaxis, and chemopreventive effects on various cancer cells. To clarify the underlying role and molecular mechanisms of OMT in human hemangioma (HA), in the present study, we examined the expression of hypoxia-inducible factor-1a (HIF-1a) and vascular endothelial growth factor (VEGF) in different phases of human HA. After HA derived endothelial cells (HDEC) were pretreated with different concentrations of OMT, cell proliferation, apoptosis, and cycle distribution were evaluated by MTT assay and flow cytometry analysis, respectively. The effects of OMT on expression of HIF-1a signaling were determined by real-time PCR and western blot assays. Our results showed that, the expression of HIF-1a and VEGF was significantly increased in proliferating phase HA, but decreased in involuting phase HA. Moreover, OMT in vitro inhibited proliferative activities and induced cell apoptosis and cycle arrest in G0/G1 phase in HA cells with decreased expression of HIF-1a, VEGF, Bcl-2, and CyclinD1, and increased expression of p53. Taken together, our findings suggest that, the expression of HIF-1a and VEGF is increased in proliferating phase HA, and OMT suppresses cell proliferation and induces cell apoptosis and cycle arrest in proliferative phase HA through inhibition of the HIF-1a signaling pathway, suggesting OMT may provide a novel therapeutic strategy for the treatment of HA.

Enhanced stability and activity with Pd-O junction formation and electronic structure modification of palladium nanoparticles supported on exfoliated montmorillonite for the oxygen reduction reaction.

Palladium has been the focus of recent research on alternative Pt catalysts for the oxygen reduction reaction (ORR). We show that the activity and stability of Pd toward the ORR can be enhanced by Pd-O-oxide covalent bonding when Pd is supported on exfoliated montmorillonite (ex-MMT) nanoplatelets.

Experimental and DFT study of thiol-stabilized Pt/CNTs catalysts.

Using a combination of experiments and density functional theory (DFT) calculations, we explored the mechanisms of the stabilization effect of the thiolized (-SH) group on the Pt/SH-CNTs catalyst. Pt particles supported on the hydroxyl functionalized CNTs (Pt/OH-CNTs) are synthesized as a baseline for comparison. Experimentally, the platinum on OH-CNTs has a stronger tendency for aggregation than that on SH-CNTs. The differences in the oxidation resistance, migration activation energy, and corrosion resistance between the Pt/SH-CNTs and Pt/OH-CNTs are calculated using DFT. The DFT calculations indicate that the -SH group enhances the oxidation resistance of the Pt cluster and CNTs and restricts Pt migration on the CNTs. DFT calculations also suggest that the enhanced stability of Pt/SH-CNTs originates from the increased interaction between Pt and SH-CNTs and the depressed d-band center of the Pt NPs. Thus, the functional groups on the CNTs used for stabilization of supported Pt NPs should provide a deposit and anchor site for Pt NPs and maintain the perfect structure of CNTs rather than destroying it.

Solitary intracranial plasmacytoma located in the spheno-clival region mimicking chordoma: a case report.

Solitary intracranial plasmacytoma (SIP) is very rare. This case report presents serial findings of SIP located in the spheno-clival region in a 54-year old female who presented with an inferior hemianopia in the right eye and an enlarged physiological blind spot in both eyes. Based on the initial diagnosis of a spheno-clival region chordoma, the tumour was partially resected by the nasal-sphenoidal sinus approach. Subsequently, the correct diagnosis of SIP was made based on the pathology and immunohistochemical staining of the tumour. The patient was treated using a whole skull-base radiation therapy protocol with 45 Gy and she was in good physical condition during the subsequent 22 months. The findings of a series of similar case reports documenting SIP in 20 cases published from 1976 to 2008 are also reviewed. Based on these case reports, the key features of SIP, including their clinical manifestations, clinical imaging characteristics, treatment and prognosis, are described.

Apoptotic markers are increased in platelets stored at 37 degrees C.

BACKGROUND: PLTs for transfusion lose viability during storage in blood banking. This loss of viability is accelerated at 37 degrees C, as is the risk of bacterial contamination, and has led to the selection of 22 degrees C as the routine storage temperature. Because PLTs contain an intact apoptotic mechanism, we sought to determine whether PLTs undergo apoptosis during storage and whether storage at 37 degrees C accelerated this process. STUDY DESIGN AND METHODS: PLT-rich plasma from PLT concentrates was stored at 37 or 22 degrees C in small aliquots or whole bags, with and without cell-permeable caspase inhibitors. Number of PLTs, pH, LDH level, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium activity were analyzed over time. PLT lysates were prepared and tested for the presence and activation of apoptotic proteins by enzyme assay and Western blotting. RESULTS: PLT viability was greatly reduced after 1 to 2 days of storage at 37 degrees C; however, signs of apoptosis were evident by 3 hours after temperature shift. In temperature-stressed PLTs only, a gradual rise in caspase-3 activity was detected that correlated with the appearance of the 17- to 20-kDa cleavage products of caspase-3. Gelsolin, a caspase-3 substrate, underwent cleavage within the same time frame. Bcl-xL and caspase-2 also declined significantly; caspase-9 activity rose. Specific caspase inhibitors could prevent caspase activation but did not improve PLT cellular viability at 37 degrees C. CONCLUSIONS: PLTs contain apoptotic proteins that are activated during PLT storage at 37 degrees C and may account for the rapid decline in PLT cellular viability. Although ineffective here, inhibition of PLT apoptosis may improve PLT cellular viability.

The class III effect of azimilide is not associated with reverse use-dependence in open-chest dogs.

Certain class III antiarrhythmic agents manifest loss of effect at short cycle lengths (CLs). This effect may limit their efficacy in the presence of tachycardia. We studied the frequency-dependent effect of azimilide (NE-10064), a new class III agent, on the right ventricular monophasic action potential (APD90) in 12 open-chest dogs. The monophasic action-potential duration at different pacing CLs (140-400 ms), during sinus rhythm, and ventricular fibrillation CL (VFCL) from left epicardial electrograms were recorded before and after increasing doses of intravenous azimilide. At pacing CL of 400 ms, APD90 was significantly prolonged after 7, 17, and 30 mg/kg of azimilide by 5.4, 7.7, and 10.7%, respectively. The extent of APD90 prolongation was independent of rate. Azimilide increased the APD90 by similar amounts at CL of 400 ms and at the fastest possible stimulation rate maintaining 1:1 capture (mean, 171 +/- 23 ms): by 2.6 +/- 8.6% and 5.6 +/- 5.9% at 2 mg/kg, 5.4 +/- 4.8% and 4.8 +/- 4.7% at 7 mg/kg, 7.7 +/- 5.6% and 9.9 +/-4.5% at 17 mg/kg, and 10.7 +/- 2.6% and 19.3 +/- 11.9% at 30 mg/kg, respectively. Azimilide caused no changes in arterial blood pressure or heart rate. Azimilide prolongs APD90 even at very short CLs. The absence of reverse use-dependence of effect on APD90 may have clinical importance.

Azimilide decreases defibrillation voltage requirements and increases spatial organization during ventricular fibrillation.

INTRODUCTION: Drugs with class III antiarrhythmic properties generally decrease defibrillation threshold (DFT). However, the concentration effect relation for this effect and drug effects on ventricular fibrillation (VF) itself are not well understood. The objectives of this study were to determine the effect of azimilide (NE-10064), a new class III agent, on DFT, and on spatial organization during VF. METHODS: Defibrillation patch electrodes were sutured to the right and left ventricular epicardium in 12 open-chest anesthetized dogs. The delayed up-down algorithm was used to measure DFT and to estimate the shock strength (voltage) with a 50% probability of successful defibrillation (V50). The magnitude squared coherence (MSC), which measures the spatial relation in the frequency domain, was measured during VF between two unipolar epicardial electrodes 3 mm apart. The V50, MSC, electrophysiologic parameters, and plasma concentrations were determined before and after four cumulative i.v. doses of azimilide (2, 7, 17, and 30 mg/kg). RESULTS: Azimilide elicited a dose dependent reduction of V50 and increase in MSC. Compared with baseline, azimilide lowered mean V50 by 2 +/- 9%, 10 +/- 18%, 11 +/- 14% and 19 +/- 5%, and increased MSC by 17 +/- 20%, 32 +/- 31%, 20 +/- 44% and 27 +/- 20% (p < 0.05 for dose effect) at 2, 7, 17 and 30 mg/kg, respectively. Mean increases in monophasic action potential duration at 90% repolarization (3-11%), ventricular effective refractory period (6-13%) at 400 msec paced cycle length, and VF cycle length (5-37%) (p < 0.01 for dose effect) were observed with the 4 increasing doses of azimilide, respectively. CONCLUSION: Azimilide significantly decreases DFT and increases coherence in VF in a dose dependent manner.

[Transcoronary chemical ablation of ventricular tachycardia after mapping of the arterial blood supply to the arrhythmogenic area (report of 2 cases)].

Transcoronary chemical ablation of ventricular tachycardia was performed in 2 patients with refractory ventricular tachycardia in Fu Wai Hospital. The procedures were successful. 1.5 ml sterilized ethanol (95%) was given to 1 patient and 0.8 ml to the other. The 2 patients were cured and no arrhythmia was found during 32-months and 4-months follow-up period respectively. One patient developed a limited inferior wall myocardial infarction after 1.5 ml ethanol. No other complications were observed. We found that after careful transcoronary mapping with saline and antiarrhythmic drugs, chemical ablation could prevent further episodes of the arrhythmia in selected high risk patients.

Transcoronary chemical ablation of ventricular tachycardia.

Transcoronary chemical ablation of ventricular tachycardia was recently performed in one patient with refractory ventricular tachycardia in our hospital. The procedure was successful. The arrhythmia was cured and no recurrence occurred in a 24-month period. The clinical application and mechanism of transcoronary chemical ablation were discussed.

Transcoronary ethanol ablation of experimental ventricular tachycardia after epicardial ice mapping and localizing.

Thirty-seven reproducible ventricular tachycardias (VTs) were induced in 19 dogs after the onset of myocardial infarction. The site of origin of VT was localized in 19 (59%) of 32 VTs by ice epicardial mapping. After 0.3-1.2 ml of 95% ethanol was injected into a small coronary artery supplying the arrhythmogenic area, VT was no longer inducible in 10 of 14 dogs. Intramyocardial ethanol (1-3 ml) was injected into the site of origin of VT in 9 dogs including 4 with VTs reinduced after intracoronary ethanol. Six of these VTs were not reinduced. Thus, the total efficacy rate was 84%. In 7 dogs, after injection of 0.4-1.2 ml (mean 0.5 ml) of 95% ethanol into a small normal coronary artery, the extent of the changes in ECG, CK-MB and pathology was found to be related to the size of myocardial damage and to the dose of ethanol. The smaller the dose of ethanol was given and the more distal the branch of coronary artery into which the ethanol was injected, the smaller the myocardial damage was. The data demonstrated that intracoronary or intramyocardial injection of ethanol may ablate the experimental VT induced by programmed heart stimulation in dogs after myocardial infarction, indicating that this approach may be useful and meaningful in some selected instances. However, it is necessary to limit the myocardial damage as far as possible.