Coronary revascularisation for postischaemic heart failure: how myocardial viability affects survival

OBJECTIVE—To assess the impact of revascularisation of viable myocardium on survival in patients with postischaemic heart failure.
METHODS—35 patients (mean (SD) age 58 (7) years) with severe heart failure (New York Heart Association (NYHA) functional class ⩾ III), mean left ventricular ejection fraction (LVEF) 24 (7)% (range 10-35%), and limited exercise capacity (peak oxygen consumption (VO₂) 15 (4) ml/kg/min) were studied. 21/35 patients had no angina. Myocardial viability was assessed with quantitative positron emission tomography and the glucose analogue ¹⁸F-fluorodeoxyglucose (FDG) (viable segment = FDG uptake ⩾ 0.25 µmol/min/g) in all patients before coronary artery bypass grafting. Patients were divided into two groups: group 1, ⩾ 8 viable dysfunctional segments (mean 12 (2), range 8-15); and group 2, < 8 viable dysfunctional segments (mean 3.5 (3), range 0-7). The two groups were comparable for age, sex, NYHA class, LVEF, and peak VO₂.
RESULTS—Two patients died perioperatively and seven patients died during follow up (mean 33 (14) months). All deaths were from cardiac causes. Kaplan-Meyer survival analysis showed 86% survival for group 1 patients versus 57% for group 2 (p = 0.03). Analysis by Cox proportional hazard model revealed three independent factors for cardiac event free survival: presence of ⩾ 8 viable segments (p = 0.006); preoperative LVEF (p = 0.002); and patient age (p = 0.01).
CONCLUSION—Revascularisation for postischaemic heart failure can be associated with good survival, which is critically dependent upon the amount of viable myocardium.


     

Dobutamine magnetic resonance imaging as a predictor of myocardial functional recovery after revascularisation

OBJECTIVE—To assess the use of dobutamine magnetic resonance imaging (MRI) as a preoperative predictor of myocardial functional recovery after revascularisation, comparing wall motion and radial wall thickening analyses by observer and semi-automated edge detection.
PATIENTS—25 men with multivessel coronary disease and resting wall motion abnormalities were studied with preoperative rest and stress MRI.
MAIN OUTCOME MEASURES—Observer analysis for radial wall thickening was compared with a normal range, while wall motion analysis used a standard four point scale. Semi-automated analysis was performed using an edge detection algorithm. Segments displaying either improved or worsened thickening or motion with dobutamine were considered viable. Postoperative rest images were performed 3-6 months after coronary artery bypass grafting (CABG) for comparison.
RESULTS—For observer analysis the values for sensitivity and specificity were 50% and 72% for wall motion, with respective values of 50% and 68% for thickening. With semi-automated edge detection the figures for motion were 60% and 73%, with corresponding values of 79% and 58% for thickening. Combining thickening and motion for the semi-automated method to describe any change in segmental function yielded a sensitivity of 71% and specificity of 70%.
CONCLUSIONS—Dobutamine MRI is a reasonably good predictor of myocardial functional recovery after CABG. The use of semi-automated edge detection analysis improved results.


Keywords: dobutamine; magnetic resonance imaging myocardial viability; coronary artery bypass grafting     

Polyelectrolyte Complex Nanoparticles Based on Methoxy Poly(Ethylene Glycol)-B-Poly (ε-Caprolactone) Carboxylates and Chitosan for Delivery of Tolbutamide

Abstract

In this study, a novel chitosan (CS)-modified nanoparticles (NPs) were developed to orally deliver tolbutamide (TOL). Methoxy poly(ethylene glycol)- b-poly(ε-caprolactone) carboxylates (mPEG₂₀₀₀-b-PCL₄₀₀₀) was synthesized via an esterification reaction. CS-modified mPEG₂₀₀₀-b-PCL₄₀₀₀-COOH NPs (CS@NPs) were fabricated by injecting mPEG₂₀₀₀-b-PCL₄₀₀₀-COOH NPs suspension (1.0?mg/mL) into CS solution (1.0?mg/mL, pH 5.0). Fourier transform infrared spectroscopy (FTIR) spectra were used to confirm the obtaining of mPEG₂₀₀₀-b-PCL₄₀₀₀-COOH. Transmission electron microscope (TEM) was carried out to observe morphology of all NPs. Nano ZS90 Malvern ParticleSizer were used to monitor the size distribution of obtained NPs. Thermogravimetry analysis (TGA) was performed to investigate the thermostability of CS@NPs. In vitro TOL release profiles were carried out in pH 1.2 and 7.4 buffers. FTIR spectra confirmed the obtaining of mPEG₂₀₀₀-b-PCL₄₀₀₀-COOH. TGA curves indicated that the protection of CS shells improved the thermostability of mPEG₂₀₀₀-b-PCL₄₀₀₀-COOH NPs. Cell tests indicated the CS@NPs had no obvious cytotoxicity, and they were easily taken up by 293T cells. In vitro release profiles showed that 91.0?±?1.9% of encapsulated TOL were released from TOL-CS@NPs in pH 7.4 buffer. Therefore, the positive potential of CS@NPs could increase their combining capacity with intestinal mucosal cells. Finally, these NPs would improve the bioavailability of hydrophobic drugs.     

The influence of laser frequency and groove distance on cell adhesion,cell viability,and antibacterial characteristics of Ti-6Al-4V dental implants treated by modern fiber engraving laser

ObjectiveMicro-nano scale surface modification of Ti-6Al-4V was investigated through the fascinated modern fiber engraving laser method. The process was performed at a high laser speed of 2000 mm/s, under different laser frequencies (20–160 kHz) and groove distances (0.5–50 μm).MethodsTopographic evaluations such as Atomic Force Microscopy (AFM) and Field Emission Scanning Electron Microscopy (FE-SEM) were used to identify the quality and regularity of patterns. The proliferation of human osteoblast-like osteosarcoma cells (MG63) was analyzed by MTT assay for up to 72 h. Also, the plate counting method was used to quantify the viability potential of the modified surface against Escherichia coli bacteria.ResultsThe cellular viability of the sample modified at the laser frequency of 20 kHz and grooving distance of 50 μm increased up to 35 and 10% compared to the non-treated and control samples, respectively. In the case of the surface modification at lower grooving distances range between 0.5–50 μm, the maximum laser frequency (160 kHz) applied leads to lower pulse’s energies and less bacterial adhesion. Otherwise, at groove distances more than 50 μm, the minimum laser frequency (20 kHz) applied reduces the laser pulse overlaps, increases the cell adhesion and antibacterial properties.SignificanceSurface modification by the fiber engraving laser process significantly enhances the cell adhesion on the surface. As a result of such roughness and cell adhesion enhancement, the surface toxicity feature diminished, and its antibacterial properties improved.     

Response of two gingival cell lines to CAD/CAM composite blocks

ObjectiveThis study aimed to investigate the influence of CAD/CAM composite materials on human gingival fibroblasts (HGF) and gingival keratinocytes (HGK).MethodsFour materials were investigated: two resin-composite blocks (RCB), Grandio Blocs (GR) and Block HC (HC); one polymer-infiltrated ceramic network (PICN) (Enamic, EN); and one conventional resin-composite, Grandioso (GND). HGF and HGK were cultured as per the supplier’s protocol (ATCC, UK). Cell proliferation and cytotoxicity were evaluated at 1, 3, 5 and 10 days using LDH and Alamar Blue assays. Indirect immunostaining was used to assess the Caspase-3 activity. Data were analysed via two-way ANOVA, one-way ANOVA and Tukey’s post hoc test (α = 0.05 for all tests).ResultsThere was significant difference in cell proliferation of the HGK and HGF cells in contact with different composite materials but no significant differences in their cytotoxicity. There was a significant effect on cell proliferation and cytotoxicity with different exposure times, for each type of resin-composite. HGF cell proliferation was higher than HGK with almost all investigated materials and at all time points. No Caspase-3 activity was detected in either cell lines.SignificanceHGK proliferation and cytotoxicity appeared to be more influenced by composite materials compared to HGF, demonstrating EN cytotoxic effects in HGK. Different manufacturing techniques of resin-composites (photo curing versus heat/pressure curing) had no significant effect on their biocompatibility.     

The role of quercetin on the survival of neuron-like PC12 cells and the expression of α-synuclein

Both genetic and environmental factors are important in the pathogenesis of Parkinson's disease. As α-synuclein is a major constituent of Lewy bodies, a pathologic hallmark of Parkinson's disease, genetic aspects of α-synuclein is widely studied. However, the influence of dietary factors such as quercetin on α-synuclein was rarely studied. Herein we aimed to study the neuroprotective role of quercetin against various toxins affecting apoptosis, autophagy and aggresome, and the role of quercetin on α-synuclein expression. PC12 cells were pre-treated with quercetin(100, 500, 1,000 μM) and then together with various drugs such as 1-methyl-4-phenylpyridinium(MPP+; a free radical generator), 6-hydroxydopamine(6-OHDA; a free radical generator), ammonium chloride(an autophagy inhibitor), and nocodazole(an aggresome inhibitor). Cell viability was determined using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltertazolium bromide(MTT) assay. Apoptosis was detected by annexin V-fluorescein isothiocyanate and propidium iodide through the use of fluorescence activated cell sorter. α-Synuclein expression was detected by western blot assay and immunohistochemistry. The role of α-synuclein was further studied by knocking out α-synuclein using RNA interference. Cell viability increased at lower concentrations(100 and 500 μM) of quercetin but decreased at higher concentration(1,000 μM). Quercetin exerted neuroprotective effect against MPP+, ammonium chloride and nocodazole at 100 μM. MPP+ induced apoptosis was decreased by 100 μM quercetin. Quercetin treatment increased α-synuclein expression. However, knocking out α-synuclein exerted no significant effect on cell survival. In conclusion, quercetin is neuroprotective against toxic agents via affecting various mechanisms such as apoptosis, autophagy and aggresome. Because α-synuclein expression is increased by quercetin, the role of quercetin as an environmental factor in Parkinson's disease pathogenesis needs further investigation.     

Ischemia-reperfusion model in rat spinal cord: cell viability and apoptosis signaling study

This work aimed at determining the ideal ischemia time in an in vitro ischemia-reperfusion model of spinal cord injury. Rat spinal cord slices were prepared and then exposed or not to oxygen deprivation and low glucose (ODLG) for 30, 45, 60, 75 and 90 minutes. Cell viability was assessed by triphenyltetrazolium (TTC), lactate dehydrogenase (LDH) release, and fluorochrome dyes specific for cell dead (ethidium homodimer) using the apotome system. Glutamate release was enzymatically measured by a fluorescent method. Gene expression of apoptotic factors was assessed by real time RT-PCR. Whereas spinal cord slices exposed to ODLG exhibited mild increase in fluorescence for 30 minutes after the insult, the 45, 60, 75 and 90 minutes caused a 2-fold increase. ODLG exposure for 45, 60, 75 or 90 minutes, glutamate and LDH release were significantly elevated. nNOS mRNA expression was overexpressed for 45 minutes and moderately increased for 60 minutes in ODLG groups. Bax/bcl-xl ratio, caspase 9 and caspase 3 mRNA expressions were significantly increased for 45 minutes of ODLG, but not for 30, 60, 75 and 90 minutes. Results showed that cell viability reduction in the spinal cord was dependent on ischemic time, resulting in glutamate and LDH release. ODLG for 45 minutes was adequate for gene expression evaluation of proteins and proteases involved in apoptosis pathways.     

Comparison of Biocompatibility of Calcium Silicate-Based Sealers and Epoxy Resin-Based Sealer on Human Periodontal Ligament Stem Cells

The aim of this study was to evaluate the biocompatibility of calcium silicate-based sealers (CeraSeal and EndoSeal TCS) and epoxy resin-based sealer (AH-Plus) in terms of cell viability, inflammatory response, expression of mesenchymal phenotype, osteogenic potential, cell attachment, and morphology, of human periodontal ligament stem cells (hPDLSCs). hPDLSCs were acquired from the premolars (n = 4) of four subjects, whose ages extended from 16 to 24 years of age. Flow cytometry analysis showed stemness of hPDLSCs was maintained in all materials. In cell viability test, AH-Plus showed the lowest cell viability, and CeraSeal showed significantly higher cell viability than others. In ELISA test, AH-Plus showed higher expression of IL-6 and IL-8 than calcium silicate-based sealers. In an osteogenic potential test, AH-Plus showed a lower expression level than other material; however, EndoSeal TCS showed a better expression level than others. All experiments were repeated at least three times per cell line. Scanning electronic microscopy studies showed low degree of cell proliferation on AH-Plus, and high degree of cell proliferation on calcium silicate-based sealers. In this study, calcium silicate-based sealers appear to be more biocompatible and less cytotoxic than epoxy-resin based sealers.