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.

     

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.     

Increased thrombin generation in splanchnic vein thrombosis is related to the presence of liver cirrhosis and not to the thrombotic event

Introduction

In recent years there have been increasing evidence associating liver disease with hypercoagulability, rather than bleeding. The aim of the study was to evaluate the haemostatic potential in patients with liver disease.

Patients and methods

We measured thrombin generation in the presence and absence of thrombomodulin in patients with portal vein thrombosis (PVT, n = 47), Budd-Chiari syndrome (BCS, n = 15) and cirrhosis (n = 24) and compared the results to those obtained from healthy controls (n = 21). Fifteen patients with PVT and 10 patients with BCS were treated with warfarin and were compared to an equal number of patients with atrial fibrillation matched for prothrombin time-international normalized ratio. We assessed resistance to thrombomodulin by using ratios [marker measured in the presence/absence of thrombomodulin].

Results

There were no differences in thrombin generation between patients on warfarin treatment and their controls. Cirrhotic patients generated more thrombin in the presence of thrombomodulin and exhibited thrombomodulin resistance compared to controls [p = 0.006 for endogenous thrombin potential (ETP) and p < 0.001 for peak thrombin and both ratios ETP and peak] and patients with non-cirrhotic PVT (p = 0.001, p = 0.006, p < 0.001, p < 0.001 for ETP, peak, ratio ETP, ratio peak, respectively). The patients with cirrhotic PVT exhibited higher ETP (p = 0.044) and peak (p = 0.02) in the presence of thrombomodulin than controls, as well as thrombomodulin resistance (ETP and peak ratios: p = 0.001).

Conclusions

Hypercoagulability and thrombomodulin resistance in patients with cirrhosis were independent of the presence of splanchnic vein thrombosis. The hypercoagulability in patients with cirrhotic PVT could have implications for considering longer or more intensive treatment with anticoagulants in this group.     

Are bony pelvis dimensions associated with levator ani defects? A case–control study

Introduction and hypothesis

Bony pelvis dimensions have been shown to differ in women with and without pelvic floor dysfunction. The goal of this study was to determine whether bony pelvis dimensions are different when comparing women with severe bilateral levator ani defects (LAD) with those with normal muscles.

Methods

This is a secondary analysis of a case–control study comparing women with and those without pelvic organ prolapse. Subjects underwent pelvic organ prolapse quantification (POP-Q) examination and were classified as either having prolapse or being normal. All underwent pelvic magnetic resonance imaging (MRI). Levator defects were assessed based on the muscles’ appearance on imaging and subjects were stratified into two groups—women with normal muscles (n?=?99) and women with severe bilateral LAD (n?=?50). Bony pelvis dimensions were measured via MRI pelvimetry. The subpubic angle, interspinous and intertuberous diameters, and the sacrococcygeal joint-to-infrapubic point (SCIPP) lengths were compared.

Results

Both groups had similar demographics. The SCIPP length was 2.5 % (3 mm) shorter in women with severe LAD than in those without defects (P?=?0.02). The SCIPP measured 4 % (5 mm) less in women with prolapse and severe LAD than in subjects with prolapse but normal muscles (P?=?0.01). Logistic regression identified SCIPP length and history of forceps delivery as being independent predictors of severe bilateral LAD.

Conclusions

Severe bilateral LAD are associated with shorter SCIPP length and forceps-assisted vaginal delivery.