Hypocretin/orexin modulates body weight and the metabolism of glucose and insulin

The hypocretin/orexin (Hcrt/orexin) unit affects the functions of the nervous, cardiovascular, gastrointestinal, and reproductive systems. Hcrt/orexin ligands and receptors have been localized to different parts of the central and peripheral nervous systems, cerebrospinal fluid and blood, exocrine (pancreas, salivary, lacrimal) as well as endocrine (pancreatic islets, pituitary, adrenal) glands. Several factors including stress, glucagon‐like peptide‐1 agonists, glutamate, nicotine, glucose, and hypoglycaemia stimulate the expression of Hcrt/orexin system, but it is inhibited by ageing, bone morphogenetic protein, hypoxia/hypercapnia, melanocortin receptor accessory protein 2, and glucagon. Literature reports show that Hcrt/orexin can significantly increase insulin secretion from normal and diabetic rat pancreata. Hcrt/orexin decreases blood glucose concentration and reduces insulin resistance partly via increased tissue expression of glucose transporter type 4. It reduces obesity by increasing browning of fat cells and energy expenditure. Taken together, Hcrt/orexin modulates obesity and the metabolism of glucose and insulin. The Hcrt/orexin system may thus be a target in the development of new therapies for the treatment of diabetes mellitus.     

Long-term mortality in patients with type 2 diabetes undergoing coronary angiography: the impact of glucose-lowering treatment

Aims/hypothesis  

The aim of this study was to analyse whether the increased mortality rates observed in insulin-treated patients with type 2 diabetes and coronary artery disease are explained by comorbidities and complications.     

Risk assessment of excess drug and sunscreen absorption via skin with ablative fractional laser resurfacing

The ablative fractional laser is a new modality used for surgical resurfacing. It is expected that laser treatment can generally deliver drugs into and across the skin, which is toxicologically relevant. The aim of this study was to establish skin absorption characteristics of antibiotics, sunscreens, and macromolecules via laser-treated skin and during postoperative periods. Nude mice were employed as the animal model. The skin received a single irradiation of a fractional CO₂ laser, using fluences of 4–10 mJ with spot densities of 100–400 spots/cm². In vitro skin permeation using Franz cells was performed. Levels of skin water loss and erythema were evaluated, and histological examinations with staining by hematoxylin and eosin, cyclooxygenase-2, and claudin-1 were carried out. Significant signs of erythema, edema, and scaling of the skin treated with the fractional laser were evident. Inflammatory infiltration and a reduction in tight junctions were also observed. Laser treatment at 6 mJ increased tetracycline and tretinoin fluxes by 70- and 9-fold, respectively. A higher fluence resulted in a greater tetracycline flux, but lower skin deposition. On the other hand, tretinoin skin deposition increased following an increase in the laser fluence. The fractional laser exhibited a negligible effect on modulating oxybenzone absorption. Dextrans with molecular weights of 4 and 10 kDa showed increased fluxes from 0.05 to 11.05 and 38.54 μg/cm²/h, respectively. The optimized drug dose for skin treated with the fractional laser was 1/70–1/60 of the regular dose. The skin histology and drug absorption had recovered to a normal status within 2–3 days. Our findings provide the first report on risk assessment of excessive skin absorption after fractional laser resurfacing.     

Effects of myocardial postconditioning on the recruitment of endothelial progenitor cells

Background: Ischemic postconditioning (PostC), brief repetitive cycles of ischemia and reperfusion during early reperfusion, is suggested to protect the myocardium in patients with stent thrombosis‐elevation myocardial infarction (STEMI) by improved endothelial dysfunction and alteration of cytokine release. These mechanisms are also of importance for the recruitment of endothelial progenitor cells (EPC), an endogenous repair mechanism for re‐endothelialization and neoangiogenesis. The aim of this study was to investigate the effect of PostC on recruitment of EPC. Methods: EPC were analyzed in 20 patients with STEMI randomized to receive four cycles of PostC following percutaneous coronary intervention (PCI) or conventional PCI. Different subpopulations of EPC were quantified immediately and on day 4 using flow cytometry. Myocardium at risk, and infarct size was determined by cardiovascular magnetic resonance. Results: There was no influence of PostC on the number of different EPC (CD34⁺, CD133⁺, CD34⁺CD133⁺, CD34⁺KDR⁺, CD34^?CD133⁺KDR⁺, CD34⁺CD133⁺KDR⁺). Left ventricular ejection fraction, myocardium at risk, and infarct size did not correlate to the mobilization of EPC. There was an inverse correlation between the symptom‐to‐balloon time and the mobilization of progenitor precursor cells (CD34⁺ cells: R =?0.527, P = 0.02; CD133⁺ cells: R =?0.624, P = 0.004; CD34⁺CD133⁺ cells: R =?0.466, P = 0.04). Discussion: Ischemic PostC did not result in improved mobilization of EPC in STEMI patients. The recruitment of progenitor cells seems to be related to the duration of ischemia rather than the size of the ischemic myocardial area. More effort is needed to understand the changes of endothelial surface markers by PostC and their role in EPC recruitment and homing. (J Interven Cardiol 2012;25:103–110)     

Photocatalytic activity of micron-scale brass on emerging pollutant degradation in water: mechanism elucidation and removal efficacy assessment

Alloys or smelted metal mixtures have served as cornerstones of human civilization. The advent of smelted copper and tin, i.e., bronze, in the 4^th millennium B.C. in Mesopotamia has pioneered the preparation of other metal composites, such as brass (i.e., mixture of copper and zinc), since the bronze age. The contemporary use of these alloys has expanded beyond using their physical strength. The catalytic chemistry of micron-scale brass or copper–zinc alloy can be utilized to effectively degrade emerging contaminants (ECs) in water, which are presenting significant risks to human health and wildlife. Here, we examine the photocatalytic activity of a commercially available micro-copper–zinc alloy (KDF® 55, MicroCuZn), made with earth abundant metals, for oxidative removal of two ECs. The micron-scale brass is independently characterized for its morphology, which confirms that it has the β-brass phase and that its plasmonic response is around 475 nm. Estriol (E3), a well-known EC, is removed from water with ultraviolet (UV) radiation catalyzed by MicroCuZn and H₂O₂–MicroCuZn combinations. The synergy between H₂O₂, UV, and MicroCuZn enhances hydroxyl radical (˙OH) generation and exhibit a strong pseudo-first-order kinetic degradation of E3 with a decay constant of 1.853 × 10⁻³ min⁻¹ (r² = 0.999). Generation of ˙OH is monitored with N,N-dimethyl-4-nitrosoaniline (pNDA) and terephthalic acid (TA), which are effective ˙OH scavengers. X-ray photoelectron spectroscopy analysis has confirmed ZnO/CuO–Cu₂O film formation after UV irradiation. The second EC studied here is Δ9-tetrahydrocannabinol or THC, a psychotropic compound commonly consumed through recreational or medicinal use of marijuana. The exceptionally high solids–water partitioning propensity of THC makes adsorption the dominant removal mechanism, with photocatalysis potentially supporting the removal efficacy of this compound. These results indicate that MicroCuZn can be a promising oxidative catalyst especially for degradation of ECs, with possible reusability of this historically significant material with environmentally-friendly attributes.

Micron-scale brass is a catalyst that can be activated with ultraviolet radiation to remove emerging contaminants from water via oxidation by hydroxyl radicals.