Stöber synthesis of salen-formaldehyde resin polymer- and carbon spheres with high nitrogen content and application of the corresponding Mn-containing carbon spheres as efficient electrocatalysts for the oxygen reduction reaction

Salen-formaldehyde (SF) resin polymer spheres were synthesized by the Stöber method from 4,4′-dihydroxysalen (N,N′-bis-(4-hydroxysalicylidene)-ethylenediamine; a tetradentate N₂O₂ Schiff base ligand) and formaldehyde. The salen precursor was prepared by condensation of ethylenediamine with 2,4-dihydroxybenzaldehyde in methanol. The SF resin colloidal spheres were also prepared by using Pluronic F127 and ammonia as a porogenic agent and catalyst, respectively (SF-P). In addition, corresponding Mn(ii)-coordinated polymer spheres of the SF-P were synthesized (SF-P-Mn(ii)). Corresponding monodispersed carbon spheres of all of the abovementioned samples were also obtained by pyrolysis technique. All of the products were characterized with conventional microscopic and spectroscopic techniques, as well as other physical methods such as BET analysis. It was found that carbonization of the SF resin spheres results in carbon spheres with specific surface areas in the range of 499–528 m² g⁻¹ and average pore sizes in the range of 2.58–3.08 nm. Nitrogen content of the SF-MW_HT (obtained hydrothermally in a methanol/water mixture), and SF-P-C@Mn (obtained from carbonization of SF-P-Mn(ii)) samples were as high as 27.5 wt% and 35.02 wt%, respectively. Finally, a glassy carbon electrode (GCE) modified with SF-P-C@Mn (SF-P-C@Mn/GCE) was prepared and its electrocatalytic activity was evaluated for oxygen reduction reaction (ORR) by linear sweep voltammetry (LSV). The LSV results showed that the SF-P-C@Mn/GCE has a higher current density and a lower negative potential in the ORR compared to GCE.

Stöber synthesis of salen-formaldehyde resin polymer- and carbon spheres.     

Relationship Between Preprocedural Lipid Levels and Periprocedural Myocardial Injury in Patients Undergoing Elective Percutaneous Coronary Intervention

BackgroundPeriprocedural myocardial injury is a predictor of cardiovascular morbidity and mortality after percutaneous coronary intervention.MethodsThe authors examined the effects of preprocedural lipid levels (low-density lipoprotein, high-density lipoprotein, and triglycerides) in 977 patients with coronary artery disease who underwent elective percutaneous coronary intervention.ResultsElevated cardiac troponin I level (≥5× the upper limit of normal) was used to indicate periprocedural myocardial injury. Serum lipid samples were collected 12 hours preprocedurally. Cardiac troponin I was collected 1, 6, and 12 hours postprocedurally. Correlations between preprocedural lipid levels and postprocedural cardiac troponin I were studied. Low-density lipoprotein levels were less than 70 mg/dL in 70% of patients and greater than 100 mg/dL in only 7.4% of patients; 13% had triglyceride levels greater than or equal to 150 mg/dL, and 96% had high-density lipoprotein levels less than 40 mg/dL. Patients with elevated cardiac troponin I had significantly lower left ventricular ejection fraction than did those with cardiac troponin I levels less than 5× the upper limit of normal (P = .01). Double-and triple-vessel disease were more common in patients with elevated cardiac troponin I (P < .002). Multivariable logistic and linear regression analyses revealed no statistically significant associations between lipid levels and postprocedural cardiac troponin I elevation, possibly because such large proportions of included patients had low levels of low-density lipoprotein (70%) and a history of statin intake (86%).ConclusionThe authors found no association between lipid profile and periprocedural myocardial injury.     

Adenosine-mediated inhibition of 5'-AMP-activated protein kinase and p38 mitogen-activated protein kinase during reperfusion enhances recovery of left ventricular mechanical function

Attenuation of excessive rates of myocardial glycolysis limits proton production and Ca(2+) overload during reperfusion and improves recovery of post-ischemic left ventricular (LV) function. In order to elucidate mechanisms underlying glycolytic inhibition by adenosine (ADO), this study tested the hypothesis that the beneficial effects of ADO are due to Ser/Thr protein phosphatase (PP)-mediated inhibition of 5'-AMP-activated protein kinase (AMPK) and phosphofructokinase-2 (PFK-2). In isolated perfused working rat hearts subjected to global ischemia (GI) and reperfusion, ADO (500μmol/l), added 5min prior to the onset of GI and present throughout reperfusion, inhibits glycolysis and proton production during reperfusion and improves post-ischemic LV work. These metabolic effects of ADO are also evident during aerobic perfusion. Assays of glycolytic intermediates show that ADO-induced glycolytic inhibition occurs at the step catalyzed by PFK-1, an effect mediated by reduced activation of PFK-2 by AMPK. The PP1 and PP2A inhibitors, cantharidin (5μmol/l) or okadaic acid (0.1μmol/l), added 10min prior to ADO prevent ADO-induced inhibition of glycolysis and AMPK, as well as ADO-induced cardioprotection. ADO also inhibits p38 MAPK phosphorylation during reperfusion in a cantharidin-sensitive manner, and pharmacological inhibition of p38 MAPK (by SB202190, 10μmol/l) during reperfusion also reduces glycolysis and is cardioprotective. These results indicate that attenuation of glycolysis during reperfusion and cardioprotection can be achieved by inhibition of the stress kinases, AMPK and p38 MAPK.     

Comparison of Mineral Trioxide Aggregate's Composition with Portland Cements and a New Endodontic Cement

The aim of this study was to compare the compositions of mineral trioxide aggregates (MTAs), Portland cements (PCs), and a new endodontic cement (NEC). Our study also investigated the surface characteristics of MTA and NEC root-end fillings when immersed in normal saline. For part I, we prepared samples of 9 brands of MTAs, PCs, and NEC. The materials were imaged and analyzed by scanning electron microscopy (SEM) and energy dispersive x-ray analysis (EDXA). In part II, 3-mm-deep root-end preparations were filled with MTA or NEC and stored in normal saline for 1 week. Samples were imaged and analyzed by SEM and electron probe microanalysis (EPMA). EDXA investigations revealed differences in the dominant compounds of NEC, PCs, and MTAs. The major components of MTA and PC are the same except for bismuth. The most significant difference was the presence of higher concentrations of Fe (minor element) in gray MTA and PC when compared with white ones. EPMA results revealed remarkably different elements in MTA compared with surrounding dentin, whereas in the NEC group the distribution patterns of calcium, phosphorous, and oxygen were comparable. NEC differs chemically from MTAs and PCs and demonstrates comparable surface composition with adjacent dentin as a root-end filling material.     

Preclinical efficacy of the c-Met inhibitor CE-355621 in a U87 MG mouse xenograft model evaluated by 18F-FDG small-animal PET.

The purpose of this study was to evaluate the efficacy of CE-355621, a novel antibody against c-Met, in a subcutaneous U87 MG xenograft mouse model using (18)F-FDG small-animal PET. METHODS: CE-355621 or control vehicle was administered intraperitoneally into nude mice (drug-treated group, n = 12; control group, n = 14) with U87 MG subcutaneous tumor xenografts. Drug efficacy was evaluated over 2 wk using (18)F-FDG small-animal PET and compared with tumor volume growth curves. RESULTS: The maximum %ID/g (percentage injected dose per gram of tissue) of (18)F-FDG accumulation in mice treated with CE-355621 remained essentially unchanged over 2 wk, whereas the %ID/g of the control tumors increased 66% compared with the baseline. Significant inhibition of (18)F-FDG accumulation was seen 3 d after drug treatment, which was earlier than the inhibition of tumor volume growth seen at 7 d after drug treatment. CONCLUSION: CE-355621 is an efficacious novel antineoplastic chemotherapeutic agent that inhibits (18)F-FDG accumulation earlier than tumor volume changes in a mouse xenograft model. These results support the use of (18)F-FDG PET to assess early tumor response for CE-355621.     

Human pharmacokinetic and dosimetry studies of [(18)F]FHBG: a reporter probe for imaging herpes simplex virus type-1 thymidine kinase reporter gene expression.

9-[4-[(18)F]fluoro-3-(hydroxymethyl)butyl]guanine ([(18)F]FHBG) has been used as a reporter probe to image expression of herpes simplex virus type-1 thymidine kinase (HSV1-tk) reporter gene in living animals. Our aim was to study the kinetics, biodistribution, stability, dosimetry, and safety of [(18)F]FHBG in healthy human volunteers, preparatory to imaging patients undergoing HSV1-tk gene therapy. METHODS: [(18)F]FHBG was synthesized with a specific activity of 37,000--444,000 GBq/mmol and a radiochemical purity > 99%. Ten healthy volunteers consented to participate in the study. A transmission scan was obtained before bolus injection of 70.3--229.4 MBq [(18)F]FHBG into a hand vein, followed by dynamic PET imaging with 4 consecutive emission scans. Warmed hand-vein blood was withdrawn at various times after injection for blood time--activity measurements. Electrocardiography, blood pressure, and blood and urine pharmacologic parameters were measured before and after injection of the [(18)F]FHBG tracer (n = 5). The stability of [(18)F]FHBG in the urine was analyzed. Attenuation-corrected images were reconstructed using the ordered-subsets expectation maximization algorithm. Image region-of-interest time-activity data were used with the MIRD program to estimate absorbed radiation dosages. RESULTS: [(18)F]FHBG had rapid blood clearance; only 8.42% +/- 4.76% (mean +/- SD) of the peak blood activity remained at approximately 30 min. The average ratio of plasma activity to whole-blood activity during the study was 0.91 +/- 0.04. Penetration of [(18)F]FHBG across the blood-brain barrier was not observed. The primary routes of clearance were renal and hepatobiliary. High activities were observed in the bladder, gut, liver, and kidneys, but <0.0002% of the injected dose per gram was observed in other tissues. In the urine, 83% of activity 180 min after injection was stable [(18)F]FHBG. Blood and urine pharmacologic parameters did not change significantly after injection of the [(18)F]FHBG tracer. The bladder absorbed the highest radiation dose. CONCLUSION: [(18)F]FHBG has the desirable in vivo characteristics of stability, rapid blood clearance, low background signal, biosafety, and acceptable radiation dosimetry in humans. This study forms the foundation for using [(18)F]FHBG in applications to monitor HSV1-tk reporter gene expression.     

A plant alkaloid,veratridine, potentiates cancer chemosensitivity by UBXN2A-dependent inhibition of an oncoprotein,mortalin-2

Veratridine (VTD), an alkaloid derived from the Liliaceae plant shows anti-tumor effects; however, its molecular targets have not been thoroughly studied. Using a high-throughput drug screen, we found that VTD enhances transactivation of UBXN2A, resulting in upregulation of UBXN2A in the cytoplasm, where UBXN2A binds and inhibits the oncoprotein mortalin-2 (mot-2). VTD-treated cancer cells undergo cell death in UBXN2A- and mot-2-dependent manners. The cytotoxic function of VTD is grade-dependent, and the combined treatment with a sub-optimal dose of the standard chemotherapy, 5-Fluorouracil (5-FU) and etoposide, demonstrated a synergistic effect, resulting in higher therapeutic efficacy. VTD influences the CD44+ stem cells, possibly through UBXN2A-dependent inhibition of mot-2. The VTD-dependent expression of UBXN2A is a potential candidate for designing novel strategies for colon cancer treatment because: 1) In 50% of colon cancer patients, UBXN2A protein levels in tumor tissues are significantly lower than those in the adjacent normal tissues. 2) Cytoplasmic expression of the mot-2 protein is very low in non-cancerous cells; thus, VTD can produce tumor-specific toxicity while normal cells remain intact. 3) Finally, VTD or its modified analogs offer a valuable adjuvant chemotherapy strategy to improve the efficacy of 5-FU-based chemotherapy for colon cancer patients harboring WT-p53.