Mixed Hyperbranched/Triblock Copolymer Micelle Assemblies: Physicochemical Properties and Potential for Drug Encapsulation

Mixed micelles have numerous advantages while requiring little to no effort in preparation. This study aims to produce mixed micelle nanostructures from a linear triblock copolymer and a hyperbranched random copolymer, and is able to be loaded with the weakly water-soluble drugs curcumin and indomethacin. Different preparation techniques are employed to produce mixed micelles comprised of Pluronic F127 block copolymer, and hyperbranched poly[(ethylene glycol) methyl ether methacrylate-co-lauryl methacrylate], H-[P(OEGMA-co-LMA)], copolymer. Few studies have dabbled in these types of coassemblies, which provides insight into how structural differences of each copolymer can affect the formation of micelles. To determine the properties of the emerging nanostructures in aqueous environments, including their size, homogeneity, and surface charge, different physicochemical techniques are used, such as light scattering and spectroscopic methods. The results reveal that the copolymers combine, and spontaneously self-assemble into mixed micelle-like nanostructures in aqueous environments, whereas both systems of neat and drug-loaded nanostructures exhibit desirable properties such as small average micelle hydrodynamic radii and low size polydispersity indices. The nanostructures that result from the effective encapsulation of curcumin exhibit outstanding stability over 169 days. The fluorescent qualities of curcumin persist after encapsulation, making the novel nanostructures excellent candidates for bioimaging applications.     

Role of asymmetrical dimethylarginine in the progression of renal disease

Asymmetric dimethylarginine (ADMA) is a naturally occurring amino acid found in tissues and cells that circulates in plasma and is excreted in urine. It inhibits nitric oxide synthases (NOs) and produces considerable cardiovascular biological effects. Several studies have suggested that plasma concentrations of ADMA provide a marker of risk for endothelial dysfunction and cardiovascular disease. In animal and in population studies ADMA has been associated with progression of CKD. Several mechanisms may be involved in this association, such as compromise of the integrity of the glomerular filtration barrier and development of renal fibrosis. This review summarizes the existing literature on the biology and physiology of ADMA focusing on its role in the progression of renal disease.     

Investigational parathyroid hormone receptor analogs for the treatment of osteoporosis

Introduction: Intermittent parathyroid hormone (PTH) administration, acting through multiple signaling pathways, exerts an osteoanabolic effect on the skeleton that surpasses the effect of other antiosteoporotic agents. However, its efficacy is limited by the coupling effect and relatively common adverse events. Thus, the development of more sophisticated PTH receptor analogs seems imperative.

Areas covered: In this review, the authors summarize the role of PTH signaling pathway in bone remodeling. The authors also summarize investigational analogs targeting this pathway, which may be potential treatments for osteoporosis.

Expert opinion: β-arrestins are multifunctional cytoplasmic molecules that are decisive for regulating intracellular PTH signaling. Recently, in preclinical studies, arrestin analogs have achieved the anabolic bone effect of PTH without an accompanying increase in bone resorption. However, it is not yet known whether these analogs have adverse effects and there are no clinical data for their efficacy to date. On the other hand, several molecules derived either from PTH and PTH-related protein (PTHrP) molecules have been developed. Alternative routes of PTH 1 – 34 delivery (oral, transdermal), the PTH analog ostabolin and the N-terminal PTHrP analogs PTHrP 1 – 36 and abaloparatide, have recently been or are currently being tested in clinical trials and are more likely to become available for use in the near future.     

Atrial High-Rate Episodes in Patients with Devices Without a History of Atrial Fibrillation: a Systematic Review and Meta-analysis

Cardiovascular Drugs and Therapy - Atrial high-rate episodes (AHREs) recorded with cardiac implantable electronic devices (CIEDs) have been associated with the development of clinical atrial...     

Solution Behavior of Hydrolyzed Gradient Methyl/Phenyl Oxazoline Copolymers and Complexation with DNA

Partial hydrolysis of 2‐methyl‐2‐oxazoline/2‐phenyl‐2‐oxazoline gradient copolymers (MPOx copolymers) results in amphiphilic copolymers containing cationic ethylene imine, neutral hydrophilic 2‐methyl‐2‐oxazoline, and hydrophobic 2‐phenyl‐2‐oxazoline segments (HMPOx copolymers). The solution behavior of the HMPOx copolymers has been investigated in water, phosphate buffer saline (PBS), and fetal bovine serum (FBS) by static, dynamic, and electrophoretic light scattering and fluorescence spectroscopy. The copolymers form stable spherical aggregates in aqueous media with positive surface charge. The aggregates are found to interact extensively with proteins in FBS solutions. Soluble HMPOx/DNA complexes have also been formed in aqueous media at certain HMPOx/DNA compositions due to electrostatic interactions. The polyplexes have been studied in terms of structure and colloidal stability.

     

Peridevice Leak Following Amplatzer Left Atrial Appendage Occlusion: Cardiac Computed Tomography Classification and Clinical Outcomes

ObjectivesThis study aimed to investigate cardiac computed tomography (CT) and transesophageal echocardiography (TEE) peridevice leak (PDL) assessments, and the clinical relevance of PDL.BackgroundPDL assessment is integral during follow-up after left atrial appendage (LAA) occlusion. Comparative studies of TEE and cardiac CT are sparse, and the clinical relevance of PDL is uncertain.MethodsThis was a single-center observational study of consecutive patients undergoing LAA occlusion with Amplatzer devices (Amplatzer Cardiac Plug/Amulet) between 2010 and 2018 (N = 415). Patients with both 8-week CT and TEE were included for analysis (n = 346). Images were analyzed by blinded investigators (K.K. and A.S.). PDL on cardiac CT was classified from grade 1 to 3, based on PDL at the device disc, device lobe, and LAA contrast patency. Primary clinical outcome was a composite of ischemic stroke, transient ischemic attack, systemic embolism, or all-cause death.ResultsPDL was present in 110 patients (32%) by TEE, with 29 (8%) >3 mm. By cardiac CT, 210 patients (61%) had PDL at the disc, with contrast patency in 204 patients (59%). A grade 3 PDL (gap at disc, lobe, and LAA contrast patency) was present in 63 patients (18%). Bland-Altman analysis showed poor agreement between CT and TEE for leak sizing. CT and TEE detected PDL was not significantly associated with worse outcome, hazard ratio: 1.82 (95 % confidence interval: 0.95 to 3.50); p = 0.07 and hazard ratio: 1.43 (95% confidence interval: 0.74 to 2.76); p = 0.28, respectively.ConclusionsPDL occurrence is substantially higher with CT compared with TEE, with a large discrepancy between modalities in leak quantification. A novel CT-based classification is proposed, yet PDL was not associated with worse clinical outcome.     

Neural underpinnings of superior action prediction abilities in soccer players

The ability to form anticipatory representations of ongoing actions is crucial for effective interactions in dynamic environments. In sports, elite athletes exhibit greater ability than novices in predicting other players’ actions, mainly based on reading their body kinematics. This superior perceptual ability has been associated with a modulation of visual and motor areas by visual and motor expertise. Here, we investigated the causative role of visual and motor action representations in experts’ ability to predict the outcome of soccer actions. We asked expert soccer players (outfield players and goalkeepers) and novices to predict the direction of the ball after perceiving the initial phases of penalty kicks that contained or not incongruent body kinematics. During the task, we applied repetitive transcranial magnetic stimulation (rTMS) over the superior temporal sulcus (STS) and the dorsal premotor cortex (PMd). Results showed that STS-rTMS disrupted performance in both experts and novices, especially in those with greater visual expertise (i.e. goalkeepers). Conversely, PMd-rTMS impaired performance only in expert players (i.e. outfield players and goalkeepers), who exhibit strong motor expertise into facing domain-specific actions in soccer games. These results provide causative evidence of the complimentary functional role of visual and motor action representations in experts’ action prediction.     

Successful Percutaneous Closure of Atrial Septal Defect via Transjugular Approach with the Cocoon Septal Occluder

The percutaneous closure of ostium secundum atrial septal defects (ASD) is a well-established procedure. Currently available devices and delivery systems are designed to be used via the femoral venous route. However, an alternative approach needs to be considered in cases of congenital or acquired caval obstruction. We describe a successful transjugular closure of a moderate sized secundum ASD with the Cocoon Septal Occluder in a 37-year-old symptomatic woman with inferior vena cava (IVC) thrombosis, using a novel deployment technique to overcome difficulties, namely maintaining stable sheath position in the left atrium. Percutaneous closure of secundum ASDs via the transjugular approach is safe, feasible and effective and can be a reasonable alternative to surgical closure in patients with failed femoral venous access and not anatomically complex atrial septal defects.     

Ausbildung eines koronaren Pseudoaneurysmas nach komplexer Koronarintervention mit Drug-eluting-Stentimplantation

We report on a 68-year-old woman with typical symptoms of angina pectoris and unspecific findings in the 12-lead surface electrocardiogram. Invasive diagnostics with coronary angiography revealed a severely calcified ostial filiform stenosis of the right coronary artery (RCA). Therefore, a complex coronary intervention was performed and a drug-eluting stent was implanted (Taxus? stent, Boston Scientific). After 6 weeks a control coronary angiography with intracoronary optical coherence tomography was performed and a new pseudoaneurysm before the RCA stent (proximal RCA) was visible. In a conference with cardiologists and cardiac surgeons (heart team) indications for cardiac surgery were confirmed. The pseudoaneurysm was removed by clipping and an aortocoronary RCA bypass was performed. The postoperative follow-up was without any complications.