A Novel Preparation Method for 5-Aminosalicylic Acid Loaded Eudragit S100 Nanoparticles

In this study, solution enhanced dispersion by supercritical fluids (SEDS) technique was applied for the preparation of 5-aminosalicylic acid (5-ASA) loaded Eudragit S100 (EU S100) nanoparticles. The effects of various process variables including pressure, temperature, 5-ASA concentration and solution flow rate on morphology, particle size, 5-ASA loading and entrapment efficiency of nanoparticles were investigated. Under the appropriate conditions, drug-loaded nanoparticles exhibited a spherical shape and small particle size with narrow particle size distribution. In addition, the nanoparticles prepared were characterized by X-ray diffraction, Differential scanning calorimetry and Fourier transform infrared spectroscopy analyses. The results showed that 5-ASA was imbedded into EU S100 in an amorphous state after SEDS processing and the SEDS process did not induce degradation of 5-ASA

A Novel Model of Atherosclerosis in Rabbits Using Injury to Arterial Walls Induced by Ferric Chloride as Evaluated by Optical Coherence Tomography as well as Intravascular Ultrasound and Histology

This study aim was to develop a new model of atherosclerosis by FeCl3-induced injury to right common carotid arteries (CCAs) of rabbits. Right CCAs were induced in male New Zealand White rabbits (n = 15) by combination of a cholesterol-rich diet and FeCl3-induced injury to arterial walls. The right and left CCAs were evaluated by histology and in vivo intravascular ultrasound (IVUS) and optical coherence tomography (OCT) examinations of 24 hours (n = 3), 8 weeks (n = 6), and 12 weeks (n = 6) after injury. Each right CCA of the rabbits showed extensive white-yellow plaques. At eight and 12 weeks after injury, IVUS, OCT, and histological findings demonstrated that the right CCAs had evident eccentric plaques. Six plaques (50%) with evident positive remodeling were observed. Marked progression was clearly observed in the same plaque at 12 weeks after injury when it underwent repeat OCT and IVUS. We demonstrated, for the first time, a novel model of atherosclerosis induced by FeCl3. The model is simple, fast, inexpensive, and reproducible and has a high success rate. The eccentric plaques and remodeling of plaques were common in this model. We successfully carried out IVUS and OCT examinations twice in the same lesion within a relatively long period of time

Inactivating hepatic follistatin alleviates hyperglycemia

Unsuppressed hepatic glucose production (HGP) contributes substantially to glucose intolerance and diabetes, which can be modeled by the genetic inactivation of hepatic insulin receptor substrate 1 (Irs1) and Irs2 (LDKO mice). We previously showed that glucose intolerance in LDKO mice is resolved by hepatic inactivation of the transcription factor FoxO1 (that is, LTKO mice)-even though the liver remains insensitive to insulin. Here, we report that insulin sensitivity in the white adipose tissue of LDKO mice is also impaired but is restored in LTKO mice in conjunction with normal suppression of HGP by insulin. To establish the mechanism by which white adipose tissue insulin signaling and HGP was regulated by hepatic FoxO1, we identified putative hepatokines-including excess follistatin (Fst)-that were dysregulated in LDKO mice but normalized in LTKO mice. Knockdown of hepatic Fst in the LDKO mouse liver restored glucose tolerance, white adipose tissue insulin signaling and the suppression of HGP by insulin; however, the expression of Fst in the liver of healthy LTKO mice had the opposite effect. Of potential clinical significance, knockdown of Fst also improved glucose tolerance in high-fat-fed obese mice, and the level of serum Fst was reduced in parallel with glycated hemoglobin in obese individuals with diabetes who underwent therapeutic gastric bypass surgery. We conclude that Fst is a pathological hepatokine that might be targeted for diabetes therapy during hepatic insulin resistance

Prevalence and Characteristics of TCFA and Degree of Coronary Artery Stenosis An OCT, IVUS, and Angiographic Study

AbstractBackgroundThe relationship between features of vulnerable plaque and angiographic coronary stenosis is unknown.ObjectivesThe purpose of this study was to systematically investigate the absolute number, relative prevalence, and characteristics of thin-cap fibroatheroma (TCFA) at different degrees of stenosis using optical coherence tomography (OCT), intravascular ultrasound, and coronary angiography.MethodsWe identified 643 plaques from 255 subjects who underwent OCT imaging in all 3 coronary arteries. They were divided into 3 groups on the basis of angiographic diameter stenosis: Group A (30% to 49%, n = 325), Group B (50% to 69%, n = 227), and Group C (>70%, n = 91).ResultsOCT showed that the absolute number of TCFA was greatest in Group A (n = 58), followed by Groups B (n = 40) and C (n = 33). However, the relative prevalence of TCFA was higher in Group C (36%) than in Groups A (18%) or B (18%) (p = 0.003 and p = 0.002, respectively). Fibrous cap of TCFA was thinner in Group C than in Groups A (p < 0.001) or B (p = 0.001). intravascular ultrasound showed that the plaque burden of TCFA was largest in Group C (80.1 ± 7.4%), compared with Groups B (67.5 ± 9.4%) and A (58.1 ± 8.4%). TCFA in Group C had a higher remodeling index than those in Group A (p = 0.002).ConclusionsThe absolute number of TCFA is 3 times greater in nonsevere stenosis than in severe stenosis. It is, however, twice as likely for a lesion to be TCFA in cases of severe stenosis than in nonsevere stenosis. Moreover, TCFA in severely-stenotic areas had more features of plaque vulnerability

Role of Optical Coherence Tomography in Diagnosis and Treatment of Patients with Acute Coronary Syndrome

Acute coronary syndrome (ACS) is the main cause of death worldwide and the leading cause of disease burden in high-income countries. ACS refers to a constellation of clinical symptoms that are compatible with acute myocardial ischemia. It describes a spectrum of clinical manifestations that result from a common pathophysiological process. The most common cause of ACS are rupture of an atherosclerotic lesion containing a large necrotic core and a thin fibrous cap followed by acute luminal thrombosis. It was thought that a high-resolution imaging modality would be ideal to detect high-risk plaques before their disruption and the formation of an occlusive thrombus. Optical coherence tomography has proven to be an invaluable tool in early detection of high-risk plaques and particularly in the understanding of ACS. This review focuses on the current evidence for the role of optical coherence tomography in the diagnosis and treatment of patients with ACS

Prevalence and prognostic significance of DNMT3A- and TET2- clonal haematopoiesis-driver mutations in patients presenting with ST-segment elevation myocardial infarction

Background Clonal haematopoiesis driven by mutations in DNMT3A or TET2 has recently been identified as a new risk factor for cardiovascular disease. Experimental studies suggest that these mutations may enhance inflammation which accelerates the disease progression. We aim to investigate the prevalence of mutations in DNMT3A and TET2 and their association with prognosis of patients with ST-segment elevation myocardial infarction (STEMI). Methods Targeted deep sequencing for DNMT3A and TET2 and inflammatory cytokines (IL-1β, IL-6, TNF-α, INF-γ) were analyzed in 485 patients with STEMI. Major adverse cardiac events (MACE) was a composite of death, myocardial infarction, stroke, or hospitalization due to heart failure. Findings Patients carrying DNMT3A- or TET2-CH-driver mutations with a variant allele frequency (VAF) ≥2% were found in 12.4% (60 of 485) of STEMI patients and experienced an increased incidence of the death (30.9% vs 15.5%, P = 0.001) and MACE (44.5% vs 21.8%, P < 0.001) compared to those who did not, during a median follow up of 3.0 (interquartile range: 2.4–3.4) years. After adjusting for confounders, mutation remained an independent predictor of death (HR = 1.967, 95% CI 1.103–3.507, P = 0.022) and MACE (HR = 1.833, 95% CI 1.154–2.912, P = 0.010). Concentrations of plasma IL-1β (P = 0.010) and IL-6 (P = 0.011) were significantly elevated in DNMT3A/TET2 VAF≥2% group. Interpretation DNMT3A- or TET2-CH-driver mutations with a VAF≥2% were observed in over 10% STEMI patients, and were significantly associated with poorer prognosis, which might be explained by higher levels of inflammatory cytokines in mutations carriers

Mining Regional Co-Occurrence Patterns for Image Classification

In the context of image classification, bag-of-visual-words mode is widely used for image representation. In recent years several works have aimed at exploiting color or spatial information to improve the representation. In this paper two kinds of representation vectors, namely, Global Color Co-occurrence Vector (GCCV) and Local Color Co-occurrence Vector (LCCV), are proposed. Both of them make use of the color and co-occurrence information of the superpixels in an image. GCCV describes the global statistical distribution of the colorful superpixels with embedding the spatial information between them. By this way, it is capable of capturing the color and structure information in large scale. Unlike the GCCV, LCCV, which is embedded in the Riemannian manifold space, reflects the color information within the superpixels in detail. It records the higher-order distribution of the color between the superpixels within a neighborhood by aggregating the co-occurrence information in the second-order pooling way. In the experiment, we incorporate the two proposed representation vectors with feature vector like LLC or CNN by Multiple Kernel Learning (MKL) technology. Several challenging datasets for visual classification are tested on the novel framework, and experimental results demonstrate the effectiveness of the proposed method

Validation of a New Animal Model of Vulnerable Plaques by Intravascular Optical Coherence Tomography In Vivo

We aimed to establish a rabbit model of vulnerable plaques (VPs) with the morphology and component characteristics of human VPs and to evaluate the microstructural features of VPs in vivo using intravascular optical coherence tomography (OCT). Twelve rabbits underwent endothelial denudation of the carotid artery and consumed a 1% high-cholesterol diet (HCD). They were equally divided into two groups: group A (modified needle injury) and group B (balloon injury). OCT was undertaken thrice before injury as well as 1 h and 12 weeks after injury. The degree of acute artery injury after endothelial denudation was detected by OCT. Twelve weeks after injury, OCT showed that both groups generated VPs which had thin fibrous caps and a large lipid core, whereas plaques in group A had smaller lipid arcs (). Histological findings demonstrated that a larger eccentricity index (EI) () and greater infiltration of macrophages () in group A than in group B. Qualitative and morphometric analyses of plaques showed a significant correlation between histological and OCT measurements. A combination of modified endothelial denudation and an HCD in rabbits produced more eccentric lesions similar to those seen in humans. These data suggest that OCT could be a useful tool for evaluation of the degree of injury and VPs in vivo