Polyglycidol, Its Derivatives, and Polyglycidol-Containing Copolymers—Synthesis and Medical Applications

Polyglycidol (or polyglycerol) is a biocompatible polymer with a main chain structure similar to that of poly(ethylene oxide) but with a –CH2OH reactive side group in every structural unit. The hydroxyl groups in polyglycidol not only increase the hydrophilicity of this polymer but also allow for its modification, leading to polymers with carboxyl, amine, and vinyl groups, as well as to polymers with bonded aliphatic chains, sugar moieties, and covalently immobilized bioactive compounds in particular proteins. The paper describes the current state of knowledge on the synthesis of polyglycidols with various topology (linear, branched, and star-like) and with various molar masses. We provide information on polyglycidol-rich surfaces with protein-repelling properties. We also describe methods for the synthesis of polyglycidol-containing copolymers and the preparation of nano- and microparticles that could be derived from these copolymers. The paper summarizes recent advances in the application of polyglycidol and polyglycidol-containing polymers as drug carriers, reagents for diagnostic systems, and elements of biosensors

Retinol-binding protein 4 (RBP-4) levels do not change after oral glucose tolerance test and after dexamethasone, but correlate with some indices of insulin resistance in humans

Introduction: Secretory products from adipocytes may contribute to deterioration in glycaemic control and increased insulin resistance (IR). Retinol-binding protein 4 (RBP-4) may increase IR in mice, with elevated levels in insulin-resistant mice and humans with obesity and type 2 diabetes. However, the mechanisms regulating RBP-4 synthesis remain not fully understood. It is not clear whether short-term glucose-induced hyperglycaemia and hyperinsulinaemia as well as glucocorticosteroid-induced increase in IR might be reflected in alterations in serum RBP-4 levels in humans. In order to investigate this, we measured serum RBP-4, glucose and insulin concentrations during 75.0 gram oral glucose tolerance test (OGTT) - Study 1, as well as before and after oral administration of dexamethasone - Study 2. Material and methods: Both studies included 35 subjects (8 males), age (mean &#177; SD) 39.1 &#177; 15.6 years, BMI 35.8 &#177; 8.7 kg/m2. Twenty-four of those subjects (5 males), age 38.7 &#177; 15.1 years, BMI 34.4 &#177; 8.3 kg/m2, had 75 gram oral glucose tolerance test (OGTT) - Study 1. Blood samples were taken before (0 minutes), and at 60 and 120 minutes of OGTT. 17 subjects (3 males, 4 subjects with type 2 diabetes), age 43.1 &#177; 18.1 years, BMI 36.7 &#177; 9.0 kg/m2 underwent screening for Cushing&#8217;s disease/syndrome (Study 2). Dexamethasone was administered in a dose of 0.5 mg every 6 hours for 48 hours. Fasting serum concentrations of RBP-4, glucose and insulin were assessed before (D0) and after 48 hours of dexamethasone administration (D2). IR was assessed by HOMA in all non-diabetic subjects and in subjects participating in study 1 also by Insulin Resistance Index (IRI), which takes into account glucose and insulin levels during OGTT. Results: Glucose administration resulted in significant increases in insulin and glucose (p < 0.0001). There was, however, no change in RBP-4 concentrations (124.1 &#177; 32 mg/ml at 0 minutes, 123 &#177; 35 mg/ml at 60 minutes and 126.5 &#177; 37.5 mg/ml at 120 minutes of OGTT, p = ns). All subjects in Study 2 achieved suppression of cortisol below 50 nmo/l. Dexamethasone administration resulted in an increase in fasting insulin (from 11.6 &#177; 6.8 to 17.1 &#177; 7.2 &#956;U/ml; p = 0.003), and an increase in HOMA (from 2.73 &#177; 1.74 to 4.02 &#177; 2.27; p = 0.015), although without a significant change in RBP-4 levels (119 &#177; 26.8 vs. 117.5 &#177; 24.8 mg/ml, p = ns). RBP-4 correlated with fasting insulin (r = 0.40, p = 0.025), fasting glucose (r = 0.41, p = 0.02) and HOMA (r = 0.43, p = 0.015), but not with IRI (r = 0.19, p = 0.31). There was, however, only a moderate correlation between HOMA and IRI (r = 0.49 [r2 = 0.24]; p = 0.006, Spearman rank correlation), while the best correlation was obtained between the product of glucose and insulin levels at 60 min of OGTT and IRI in a non-linear model (r = 0.94 [r2 = 0.88]; pWstęp: Niektóre substancje syntetyzowane przez adipocyty mogą zwiększać insulinooporność oraz nasilać zaburzenia tolerancji glukozy. Białko wiążące retinol 4 (RBP-4) nasila insulinooporność u myszy, zaś podwyższone stężenia RBP-4 obserwuje się u myszy z insulinoopornością oraz u osób z otyłością i cukrzycą typu 2. Mechanizmy regulujące syntezę RBP-4 nie są do końca poznane. Między innymi nie howiadomo czy krótkotrwała hiperglikemia i hiperinsulinemia po podaniu glukozy, jak również zwiększona insulinooporność wyidukowana glukokortykosteroidami mogą w istotny sposób zmienić stężenie RBP-4 w surowicy u ludzi. W związku z tym autorzy artykułu ocenili stężenie RBP-4, glukozy i insuliny w teście doustnego obciążenia glukozą (75 g) (OGTT) - badanie 1, oraz przed i po doustnym podaniu deksametazonu - badanie 2. Materiał i metody: W obu badaniach uczestniczyło 35 osób (8 mężczyzn) w wieku 39,1 &#177; 15,6 lat, BMI 35,8 &#177; 8,7 kg/m2 (średnia &#177; SD). Spośród nich u 24 osób (5 mężczyzn) w wieku 38,7 &#177; 15,1 lat, BMI 34,4 &#177; 8,3 kg/m2 wykonano OGTT (badanie 1). Krew pobierano przed (0 minuta) oraz w 60. i 120. minucie OGTT. Badanie 2 objęło 17 osób (3 mężczyzn, 4 osoby z cukrzycą typu 2) poddanych badaniu przesiewowemu pod kątem choroby/zespołu Cushinga w wieku 43,1 &#177; 18,1 lat, BMI 36,7 &#177; 9,0 kg/m2. Deksametazon podawano co 6 godzin w dawce 0,5 mg przez 48 godzin. Stężenia RBP-4, glukozy i insuliny w surowicy oznaczono na czczo przed (D0) i po 48 godzinach podawania deksametazonu (D2). U osób niechorujących na cukrzycę IR oceniano metodą HOMA, zaś w badaniu 1 również według Insulin Resistance Index (IRI) obliczanego na podstawie zmian stężeń insuliny i glukozy podczas OGTT. Wyniki: Podczas OGTT w badaniu 1 wzrosły stężenia insuliny i glukozy (p < 0,001), przy braku istotnych zmian stężeń RBP-4 (124,1 &#177; 32 mg/ml w 0 min, 123 &#177; 35 mg/ml w 60. min i 126,5 &#177; 37,5 mg/ml w 120. min OGTT, p = ns). W badaniu 2 u wszystkich osób uzyskano supresję stężenia kortyzolu do wartości poniżej 50 nmo/l. Skutkiem podania deksametazonu był wzrost stężeń insuliny na czczo (z 11,6 &#177; 6,8 do 17,1 &#177; 7,2 &#956;U/ml; p = 0,003) oraz wzrost współczynnika HOMA (z 2,73 &#177; 1,74 do 4,02 &#177; 2,27; p = 0,015). Nie zaobserwowano jednak istotnych zmian stężeń RBP-4 (119 &#177; 26,8 mg/ml vs. 117,5 &#177; 24,8 mg/ml, p = ns). Stężenia RBP-4 korelowały z insulinemią na czczo (r = 0,40, p = 0,025), glukozą na czczo (r = 0,41, p = 0,02) oraz z HOMA (r = 0,43, p = 0,015), lecz już nie z IRI (r = 0,19, p = 0,31). Stwierdzono obecność korelacji pomiedzy indeksami insulinooporności HOMA i IRI (r = 0.49 [r2 = 0,24], p = 0,006, współczynnik korelacji rang Spearmana), lecz znacznie silniejszą korelację obserwowano dopiero miedzy IRI a iloczynem stężeń insuliny i glukozy w 60. minucie OGTT (r = 0,94 [r2 = 0,88];

Long-Term X-ray Variability in GX 354-0

We report for the first time the detection of long-term X-ray variability in the bright bulge source GX 354-0 (=4U 1728-34) observed with the All Sky Monitor (ASM) on board the Rossi X-Ray Timing Explorer (RXTE). The 2-year RXTE ASM database reveals significant power at ~72 days. Similar behaviour was seen in the 6-year Ariel 5 ASM database, but at a period of ~63 days. The timescales and light curves resemble the ~78 days modulation seen in Cyg X-2 and we therefore interpret this modulation in GX 354-0 as a super-orbital effect.Comment: 9 pages, 3 figures, accepted for publication in New Astronom

Preparation and optical properties of novel bioactive photonic crystals obtained from core-shell poly(styrene/α-tert-butoxy-ω-vinylbenzyl-polyglycidol) microspheres

Optical properties of polymer microspheres with polystyrene cores and polyglycidol-enriched shells poly(styrene/α-tert-butoxy-ω-vinylbenzyl-polyglycidol) (P(S/PGL) particles with number average diameters Dn determined by scanning electron microscopy equal 237 and 271 nm), were studied before and after immobilization of ovalbumin. The particles were synthesized by emulsifier-free emulsion copolymerization of styrene and polyglycidol macromonomer (poly(styrene/α-tert-butoxy-ω-vinylbenzyl-polyglycidol)) initiated with potassium persulfate. Molar fraction of polyglycidol units in the interfacial layer of the microspheres determined by XPS was equal 42.6 and 34.0%, for the particles with Dn equal 137 and 271 nm, respectively. Colloidal crystals from the aforementioned particles were prepared by deposition of particle suspensions on the glass slides and subsequent evaporation of water. It was found that optical properties of colloidal crystals from the P(S/PGL) microspheres strongly depend on modification of their interfacial layer by covalent immobilization of ovalbumin. The coating of particles with ovalbumin resulted in decreasing their refractive index from 1.58 to 1.52

Type-I bursts within outbursts of IGR J17473-2721

Two outbursts were observed by RXTE in the history of the atoll source IGR J17473-2721. During the most recent outburst in 2008, the source showed a complete series of spectral states/transitions. The neutron star system was prolific in type-I X-ray bursts, and we investigate them in the context of complete outbursts evolution. A total exposure of ~ 309 ks was collected by RXTE during the two outbursts of IGR J17473-2721. We carried out a systematic search for type-I bursts in this data set. For each burst found, we investigated the burst profile, the peak flux, and their dependence on the accretion rate along the evolution of the outbursts. Eighteen type-I X-ray bursts were found from IGR J17473-2721: two from the outburst in 2005 and the other 16 from the recent outburst in 2008. Among them, 3 bursts show photospheric radius expansion (PRE). The distance to the source is estimated as 6.4 kpc with a 15% uncertainty based on the three bursts that show PRE. In the recent outburst, there are 6 bursts showing up in the low/hard state prior to the state transition to a high/soft state, 3 bursts at the end phase of the high/soft state, and 7 in the following low/hard state. The blackbody radius of these bursts presents a variety of interesting features. We find that at the end of the recent outburst, the profile of the blackbody radius is anti-correlated with the blackbody temperature and the burst flux. The durations of the type-I burst are found to correlate with the Eddington ratio and to have two parallel evolution groups. Along the decreasing Eddington ratio, the burst duration decreases and ends in each group the PRE bursts occurred. This provides new clues to the type-I bursts in the context of outbursts for atoll XRBs.Comment: in press at A &

Registered nurses in expanded roles improve care in nursing homes: Swiss perspective based on the modified Delphi method

To define both competencies and envisaged outcomes for registered nurses in expanded roles in Swiss nursing homes to be implemented and evaluated within a new model of care.; In regions where Advanced Practice Nurses are rare or absent, registered nurses take up clinical leadership and expanded roles. To allow effective implementation, monitoring and evaluation of these nurses, stakeholders need a shared understanding of the competencies they require and what outcomes they should achieve.; RAND/UCLA Appropriateness Method - a modified Delphi method.; A critical literature review and case studies were conducted to identify possible competencies and outcomes for registered nurses in expanded roles. In 2017, a two-round rating process and an in-person panel discussion was completed by a group of multi-professional stakeholders.; Two rounds generated 190 competencies and 72 outcomes relevant to registered nurses in expanded roles.; The relevant competencies and outcomes of registered nurses in expanded roles indicate their support for care teams and development of nursing care in nursing homes. Their geriatric expertise allows them to function as role models and innovators, reinforcing overall perceptions of nursing as a profession. These nurses are especially important in countries and settings where Advanced Practice Nurses are scarce or unavailable.; The identified competencies clarify the duties of expanded-role registered nurses, thereby differentiating them from other care providers. Although conducted in the Swiss healthcare system, our methods and findings can be adapted to other healthcare settings. The results of this study will guide the development of an educational programme in a multi-centre study to reduce avoidable hospitalizations, while the defined outcomes guide the evaluation of their impact

Equine Metabolic Syndrome Affects Viability, Senescence, and Stress Factors of Equine Adipose-Derived Mesenchymal Stromal Stem Cells: New Insight into EqASCs Isolated from EMS Horses in the Context of Their Aging

Currently, equine metabolic syndrome (EMS), an endocrine disease linked to insulin resistance, affects an increasing number of horses. However, little is known about the effect of EMS on mesenchymal stem cells that reside in adipose tissue (ASC). Thus it is crucial to evaluate the viability and growth kinetics of these cells, particularly in terms of their application in regenerative medicine. In this study, we investigated the proliferative capacity, morphological features, and accumulation of oxidative stress factors in mesenchymal stem cells isolated from healthy animals (ASCN) and horses suffering from EMS (ASCEMS). ASCEMS displayed senescent phenotype associated with β-galactosidase accumulation, enlarged cell bodies and nuclei, increased apoptosis, and reduced heterochromatin architecture. Moreover, we observed increased amounts of nitric oxide (NO) and reactive oxygen species (ROS) in these cells, accompanied by reduced superoxide dismutase (SOD) activity. We also found in ASCEMS an elevated number of impaired mitochondria, characterized by membrane raptures, disarrayed cristae, and vacuole formation. Our results suggest that the toxic compounds, accumulating in the mitochondria under oxidative stress, lead to alternations in their morphology and may be partially responsible for the senescent phenotype and decreased proliferation potential of ASCEMS