Treatment strategies for hypertension in patients with type 1 diabetes

ABSTRACT

Introduction

Type 1 diabetes mellitus (T1DM) is a chronic, autoimmune disease that is characterized by total absence of insulin production. Hypertension is a common comorbidity in T1DM with complex pathophysiology, while it is also a well-recognized risk factor for the development of cardiovascular disease (CVD), as well as other microvascular diabetic complications.     

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.     

Reducing alcohol use among 9th grade students: 6 month outcomes of a brief,Web-based intervention

This study tested a brief, Web-based personalized feedback program aimed at reducing alcohol use and alcohol-related consequences among 9th grade students (N = 513). Results indicated no differences between the control group and intervention group on either frequency of drinking or alcohol-related consequences at the 6-month follow-up. Reductions in alcohol use and the associated consequences found at the 3-month follow-up were not sustained across the academic year. Results indicate that brief, Web-based feedback programs may not be sufficient to provide a sustained impact on alcohol use and alcohol-related consequences over time, suggesting either booster sessions or adjunctive interventions, such as parent-based interventions, may be warranted for this age group.     

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.

     

Somatostatin receptor scintigraphy before and after treatment with somatostatin analogues in patients with thyroid eye disease.

Octreotide, a potent synthetic long-acting somatostatin analogue, has been shown to have a beneficial effect in thyroid eye disease (TED). Orbital scintigraphy using ocetreoscan-111 is a useful study, which can be used to visualize somatostatin-receptor-bearing cells and also to select patients who might benefit from octreotide therapy. One major limitation of this therapy is that the drug must be administered parenterally and used several times daily. Lanreotide, a new somatostatin analogue, has a much longer duration of action in comparison with octreotide, and has recently been found to have a beneficial effect in the treatment of thyroid eye disease. The aim of this study was to investigate the orbital Indium-111-pentetreotide activity after treatment with octreotide and lanreotide in patients with thyroid ophthalmopathy. Fourteen patients were studied. 12 with bilateral and 2 with unilateral thyroid eye disease, (10 females and 4 males) and all with moderately severe symptoms of ophthalmopathy. All were treated with antithyroid drugs and were euthyroid at the time of the study. All patients were investigated with orbital scintigraphy using octreoscan-111 and selected for study on the basis of a positive octreoscan. Five patients received 30 mg lanreotide intramuscularly once every 2 weeks over a period of 3 months, and 5 patients received octreotide 100 microg subcutaneously thrice daily for 3 months. Four patients served as controls and received no treatment. The octreoscan-111 scintigraphy was repeated in all patients 3 months after the first examination. The NOSPECS classification and the clinical activity score (CAS) of thyroid ophthalmopathy were also evaluated before and 3 months after the initiation of treatment. All patients who received treatment had a negative follow-up octreoscan while controls had a positive octreoscan. NOSPECS score and CAS were improved with treatment, but unchanged in control patients. The reduced uptake of octreoscan may be the result of blocking of somatostatin receptors, or reduction in receptor-expressing tissues, downregulation of somatostatin receptors in target tissues, or a combination of these factors.     

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.