Vasoactive effects of stable aqueous suspensions of single walled carbon nanotubes in hamsters and mice

Single-walled carbon nanotubes synthesized with iron (Fe-SWCNT) or gadolinium (Gd-SWCNT) show promise as high performance multimodal contrast and drug-delivery agents. Our purpose was to evaluate potential vasoactive effects of SWCNT. Stable aqueous solutions of Fe-SWCNTs or Gd-SWCNTs were made using the biocompatible amphiphilic polymer N-(carbonyl-methoxypolyethyleneglycol 2000)-1,2-distearoylsn-glycero-3- phosphoethanolamine (PEG-DSPE). Both aggregated and non-aggregated (sonicated) formulations were tested. The initial vasoactivity of the formulations and their potential for inducing pro-inflammatory endothelial dysfunction were investigated in the hamster cheek pouch and murine cremaster muscle intravital microscopy models. These models provide an assay to test several formulations/dosages in a paired fashion. Abluminal exposure to small arterioles exposes both endothelial and vascular smooth muscle cells. Using abluminal exposures of dosages that would approximate the first pass of an i.v. bolus injection, both Fe-SWCNTs and Gd-SWCNTs were immediately vasoactive. Aggregated formulations induced dilation and non-aggregated formulations induced constriction in both hamsters and mice. Endothelial dysfunction was evident after exposure to either aggregated or non-aggregated forms. General loss of dilator capability was seen after exposure to non-aggregated but not aggregated forms. Thus concentrations mimicking bolus dosing of PEG-DSPE coated SWCNT induce both acute and chronic vascular responses.     

MRI texture analysis parameters of contrast-enhanced T1-weighted images of Crohn’s disease differ according to the presence or absence of histological markers of hypoxia and angiogenesis

Purpose

To investigate if texture analysis parameters of contrast-enhanced MRI differ according to the presence of histological markers of hypoxia and angiogenesis in Crohn’s disease (CD).

Methods

Seven CD patients (mean age 38 (19–75), 3 male)) undergoing ileal resection underwent 3T MR enterography including axial ultrafast spoiled gradient-echo T1 post IV gadolinium chelate. Regions of interest were placed in bowel destined for resection and registered to trans-mural histological sections (n = 28 across 7 bowel sections) via MRI of the resected specimen. Microvessel density (MVD) and staining for markers of hypoxia (HIF 1α) and angiogenesis (VEGF) were performed. Texture analysis features were derived utilizing an image filtration-histogram technique at spatial scaling factor (SSF) 0–6 mm, including mean, standard deviation, mean of positive pixels, entropy, kurtosis and skewness and compared according to the presence or absence of histological markers of hypoxia/angiogenesis using Mann–Whitney U/Kruskal–Wallis tests and with the log of MVD using simple linear regression.

Results

Mean, standard deviation and mean of positive pixels were significantly lower in sections expressing VEGF. For example at SSF 6 mm, median (inter-quartile range) of mean, standard deviation and mean of positive pixels in those with VEGF expression were 150.1 (134.7), 132.4 (49.2) and 184.0 (91.4) vs. 362.5 (150.2), 216.3 (100.1) and 416.6 (80.0) in those without (p = 0.001, p = 0.004 and p = 0.001), respectively. There was a significant association between skewness and MVD (ratio 1.97 (1.15–3.41)) at SSF = 2 mm.

Conclusions

Contrast-enhanced MRI texture analysis features significantly differ according to the presence or absence of histological markers of hypoxia and angiogenesis in CD.

     

Mn4+-activated Li3Mg2SbO6 as an ultrabright fluoride-free red-emitting phosphor for warm white light-emitting diodes

In this paper, we report on highly efficient Mn⁴⁺-activated double perovskite Li₃Mg₂SbO₆ (LMS) red-emitting phosphors. These LMS:Mn⁴⁺ phosphors can be efficiently excited over a broad wavelength band from 235 nm to 600 nm peaking at 344 nm and 469 nm, and exhibited an intense red emission band with a range from 600 nm to 800 nm centered around 651 nm. The optimal Mn⁴⁺ doping concentration of LMS:Mn⁴⁺ was 0.6 mol% and its internal quantum efficiency can reach as high as 83%. Besides, the thermal quenching effect on the optical property was also analyzed. Finally, a warm white light-emitting diode (WLED) lamp was fabricated by using a 454 nm InGaN blue LED chip combined with a blend of YAG:Ce³⁺ yellow phosphors and the as-prepared LMS:0.6% Mn⁴⁺ red phosphors, which showed bright white light with CIE chromaticity coordinates (0.4093, 0.3725), correlated color temperature (CCT = 3254 K), color rendering index (CRI = 81) and luminous efficacy (LE = 87 lm/W).

Mn⁴⁺-activated Li₃Mg₂SbO₆ red-emitting phosphor with internal quantum efficiency as high as 83% was developed for blue-pumped warm-white light-emitting diodes.     

Implementing a pathway for the management of acute coronary syndrome leads to improved compliance with guidelines and a decrease in angina symptoms

We describe our experience with the Advanced Cardiac Admission Program (ACAP) at our institution. The ACAP program is a hospital-wide implementation of critical pathways-based management of all cardiac patients. Data review of patients admitted for acute coronary syndromes from the ACAP-PAIN database and a comparative study of outcomes before and after implementation of the pathways-based assessment and treatment protocols. In the pre-ACAP and post-ACAP patient groups, antiplatelet use at admission improved from 50% to 75% (p<.01), ACE-I use improved from 32% to 54% (p<.0001), statins use increased from 35% to 62% (p<.0001), and smoking cessation awareness increased from 15% to 86% (p<.0001). At 1-year follow-up, 84% of patients with CAD were treated with statins, and 47% had LDL cholesterol <100 mg/dL, compared with 20% and 9%, respectively, with conventional treatment before ACAP implementation (p<.0001). Recurrent angina symptoms and nonfatal myocardial infarction rates decreased from 28.5% to 13% (p = .02), and 15% to 5% (p = 0.03), respectively. Pathway-based programs like ACAP significantly enhance administration of guidelines-based cardioprotective medications both during hospital stay and at 1-year follow-up.     

Inducible lethal ventricular arrhythmias in swine with pacing-induced heart failure

Introduction: Rapid pacing-induced heart failure provides an excellent animal model for the study of heart failure. We studied the development of ventricular tachyarrhythmias using programmed stimulation in a pacing-induced heart failure model. We also studied action potential characteristics and the relationship between action potential and heart rate. Methods and results: Ten pigs were instrumented and were studied before the onset and every week after rapid pacing was instituted. Weekly echocardiograms and programmed stimulation were done in a sedated state. In vitro electrophysiologic studies were done on left ventricular myocardium in 4 heart-failure animals and 4 controls. All animals developed progressive heart failure with left ventricular dilatation and reduced percentage fractional shortening. No arrhythmias were induced at baseline or the first and second weeks. Ventricular fibrillation was induced in one animal on the third week and 4 animals on week 4, while there was no appreciable worsening in echocardiographic indices of ventricular dysfunction between weeks 3 and 4. Ventricular effective refractory period was unchanged during the 4 weeks. In vitro studies showed action potential prolongation in heart failure myocardium. However, action potential duration at pacing rates > 100 bpm were similar to controls. No early or delayed afterdepolarizations were observed. Conclusion: This study demonstrated an increased susceptibility to ventricular fibrillation with the development of heart failure which was not related to the degree of ventricular disfunction. Also, the normalization of action potential duration at higher heart rates suggests that the increased incidence of inducible ventricular fibrillation in this model may not be solely due to prolonged action potential duration. Received: 4 January 1999, Returned for 1. revision: 29 January 1999, 1.Revision received: 26 May 1999, Accepted: 15 June 1999     

Fatal aortic rupture during balloon dilatation of recoarctation.

In an eight year old boy with a patch aortoplasty, the aorta ruptured during balloon angioplasty for recoarctation. At necropsy a 1.5 cm long, full thickness tear and a separate, smaller, intimal tear were found. Histological examination showed thinning of the elastic laminae of the aorta. Angioplasty for recoarctation may be dangerous in patients with a patch aortoplasty.