Coronary microvascular dysfunction in diabetes mellitus: A review

The exploration of coronary microcirculatory dysfunction in diabetes has accelerated in recent years. Cardiac function is compromised in diabetes. Diabetic patients manifest accelerated atherosclerosis in coronary arteries. These data are confirmed in diabetic animal models, where lesions of small coronary arteries have been described. These concepts are epitomized in the classic microvascular complications of diabetes, i.e. blindness, kidney failure and distal dry gangrene. Most importantly, accumulating data indicate that insights gained from the link between inflammation and diabetes can yield predictive and prognostic information of considerable clinical utility. This review summarizes the evidence for the predisposing factors and the mechanisms involved in diabetes, and assesses the current state of knowledge regarding the triggers for inflammation in this disease. We evaluate the roles of hyperglycemia, oxidative stress, polyol pathway, protein kinase C, advanced glycation end products, insulin resistance, peroxisome proliferator-activated receptor-γ, inflammation, and diabetic cardiomyopathy as a “stem cell disease”. Furthermore, we discuss the mechanisms responsible for impaired coronary arteriole function. Finally, we consider how new insights in diabetes may provide innovative therapeutic strategies

Evaluation of the Short-Term Effects of Antimicrobial Stewardship in the Intensive Care Unit at a Tertiary Hospital in China

<div><p>Antibiotic abuse can lead to antibiotic resistance, which is a severe problem in China. The purpose of this study is to evaluate the short-term effects of antimicrobial stewardship strategies, including formulary restriction, preauthorization, perioperative quinolone restriction, and control of total antibiotic consumption in the ICU at a tertiary hospital in China. After implementation of antimicrobial stewardship, the total antibiotic consumption in the ICU significantly decreased. The defined daily doses (DDDs) per 100 patient-days decreased from 197.65 to 143.41; however, the consumption of cephalosporins increased from 53.65 to 63.17 DDDs. Significant improvements in resistance to amikacin, gentamicin, ciprofloxacin, ofloxacin, ceftriaxone, ceftazidime, and piperacillin in Enterobacteriaceae and resistance to ceftazidime, imipenem, and meropenem in non-fermenting Gram-negative rods were observed. In addition, the initial use of no antibiotics or of a single antibiotic significantly increased (P<0.001) and the use of two antibiotics in combination significantly decreased (P<0.001). Our results demonstrate that implementation of antimicrobial stewardship in a short period in the ICU dramatically reduced antibiotic consumption and significantly improved antibiotic resistance, which leads to more reasonable antibiotic selections by ICU physicians.</p></div

Changes of percentage of bacterial isolates with antibiotic resistance (%) after antimicrobial stewardship.

<p>Changes of percentage of bacterial isolates with antibiotic resistance (%) after antimicrobial stewardship.</p

Comparison of the ICU physicians' initial antibiotic selection before and after antimicrobial stewardship.

<p>Initial antibiotic combination therapy in ‘before’ and ‘after’ period: χ² = 217.924, P<0.001.</p>1<p>Before antimicrobial stewardship, χ² = 3.339, P = 0.297.</p>2<p>After antimicrobial stewardship, χ² = 8.487, P = 0.012.</p

Flow chart of antimicrobial stewardship strategies applied in the ICU at a tertiary hospital in China.

<p>These strategies primarily included formulary restriction, preauthorization, perioperative quinolone restriction, and control of total antibiotic consumption.</p

Exploring diagnostic potentials of radioiodinated sennidin A in rat model of reperfused myocardial infarction

Non-invasive "hot spot imaging" and localization of necrotic tissue may be helpful for definitive diagnosis of myocardial viability, which is essential for clinical management of ischemic heart disease. We labeled Sennidin A (SA), a naturally occurring median dianthrone compound, with (131)I and evaluated (131)I SA as a potential necrosis-avid diagnostic tracer agent in rat model of reperfused myocardial infarction. Magnetic resonance imaging (MRI) was performed to determine the location and dimension of infarction. (131)I-SA was evaluated in rat model of 24-hour old reperfused myocardial infarction using single-photon emission computed tomography/computed tomography (SPECT/CT), biodistribution, triphenyltetrazolium chloride (TTC) histochemical staining, serial sectional autoradiography and microscopy. Gamma counting revealed high uptake and prolonged retention of (131)I SA in necrotic myocardium and fast clearance from non-targeted tissues. On SPECT/CT images, myocardial infarction was persistently visualized as well-defined hotspots over 24h, which was confirmed by perfect matches of images from post-mortem TTC staining and autoradiography. Radioactivity concentration in infarcted myocardium was over 9 times higher than that of the normal myocardium at 24h. With favorable hydrophilicity and stability, radioiodinated SA may serve as a necrosis-avid diagnostic agent for assessment of myocardial viability.publisher: Elsevier articletitle: Exploring diagnostic potentials of radioiodinated sennidin A in rat model of reperfused myocardial infarction journaltitle: International Journal of Pharmaceutics articlelink: http://dx.doi.org/10.1016/j.ijpharm.2015.08.046 content_type: article copyright: Copyright © 2015 Elsevier B.V. All rights reserved.status: publishe

Cell Membrane-Anchored DNA Nanoinhibitor for Inhibition of Receptor Tyrosine Kinase Signaling Pathways via Steric Hindrance and Lysosome-Induced Protein Degradation

Receptor tyrosine kinase (RTK) plays a crucial role in cancer progression, and it has been identified as a key drug target for cancer targeted therapy. Although traditional RTK-targeting drugs are effective, there are some limitations that potentially hinder the further development of RTK-targeting drugs. Therefore, it is urgently needed to develop novel, simple, and general RTK-targeting inhibitors with a new mechanism of action for cancer targeted therapy. Here, a cell membrane-anchored RTK-targeting DNA nanoinhibitor is developed to inhibit RTK function. By using a DNA tetrahedron as a framework, RTK-specific aptamers as the recognition elements, and cholesterol as anchoring molecules, this DNA nanoinhibitor could rapidly anchor on the cell membrane and specifically bind to RTK. Compared with traditional RTK-targeting inhibitors, this DNA nanoinhibitor does not need to bind at a limited domain on RTK, which increases the possibilities of developing RTK inhibitors. With the cellular-mesenchymal to epithelial transition factor (c-Met) as a target RTK, the DNA nanoinhibitor can not only induce steric hindrance effects to inhibit c-Met activation but also reduce the c-Met level via lysosome-mediated protein degradation and thus inhibition of c-Met signaling pathways and related cell behaviors. Moreover, the DNA nanoinhibitor is feasible for other RTKs by just replacing aptamers. This work may provide a novel, simple, and general RTK-targeting nanoinhibitor and possess great value in RTK-targeted cancer therapy

PREPARATION OF GRADATED NANO-TRANSIENT LAYER AT INTERFACE BETWEEN DEPOSITED FILM AND SUBSTRATE BY HIGH-INTENSITY PULSED ION BEAM IRRADIATION

We prepared gradated nano-transient layers at different interfaces between deposited film and substrates by high-intensity pulsed ion beam (HIPIB) irradiation. The deposited film was (Al–Si) alloy and substrates were Ni and Ti, respectively. The gradated nano-transient layers at different interfaces were measured by Rutherford backscattering, its spectra were solved by SIMNRA code and then the microstructures of the gradated nano-transient layers at the interfaces of these two irradiated samples were obtained. The experimental results were analyzed by STEIPIB code. The formation of the gradated distribution of element contents in nano-transient layer at the interface can eliminate the abrupt changes of thermal and elastic characteristics at the interface. And, it can greatly reduce the mismatch of thermal expansion coefficients and Young's modulus at the interface between deposited film and substrate. Thus, after the formation of the gradated nano-transient layer, the adhesion at the interface between different materials can be enhanced and the level of thermal stresses can also be reduced in the case of thermal loading.Interface, gradated nano-transient layer, microstructure, HIPIB