Dopamine in the nucleus accumbens shell controls systemic glucose metabolism via the lateral hypothalamus and hepatic vagal innervation in rodents.

Background: Growing evidence demonstrates the role of the striatal dopamine system in the regulation of glucose metabolism. Treatment with dopamine antagonists is associated with insulin resistance and hyperglycemia, while dopamine agonists are used in treatment of type 2 diabetes. The mechanism underlying striatal dopamine effects in glucose metabolism, however is not fully understood.

Polyisobutylene-based glycopolymers as potent inhibitors for insulin aggregation.

A family of amphiphilic diblock copolymers containing a hydrophobic polyisobutylene (PIB, = 1000 g mol) segment and a hydrophilic block with sugar pendants has been synthesized by combining living cationic and reversible addition-fragmentation chain transfer (RAFT) polymerization techniques; to explore their potential in insulin fibrillation inhibition. The glucose content in the hydrophilic segment has been tailor-made from 20 to 57 units to prepare block copolymers. The removal of the acetates from the pendent glucose units resulted in amphiphilic block copolymers that generated micellar aggregates in aqueous media.

Low Dopamine D2 Receptor Increases Vulnerability to Obesity Via Reduced Physical Activity, Not Increased Appetitive Motivation.

Background: The dopamine D2 receptor (D2R) has received much attention in obesity studies. Data indicate that D2R is reduced in obesity and that the TaqA1 D2R variant may be more prevalent among obese persons. It is often suggested that reduced D2R generates a reward deficiency and altered appetitive motivation that induces compulsive eating and contributes to obesity.

Long-term in vitro hydrolytic stability of thermoplastic polyurethanes.

Long-term in vitro stability of thermoplastic polyurethanes (TPUs) was studied for up to 52 weeks in phosphate buffer solution at 37, 55, and 80°C. Water uptake, molecular weights, and tensile properties were measured at regular intervals of 4, 8, 16, 32, and 52 weeks. The rate of molecular weight reduction increased with increasing temperature, and after 52 weeks at 80°C, all commercial polycarbonate (Bionate-55D, Quadrathane-80A, and Chronoflex-80A), poly(dimethylsiloxane) (ElastEon-2A) and polyether (Elasthane-55D) TPUs showed significant (43-51%) molecular weight (Mn ) reduction.

Polyisobutylene-Based pH-Responsive Self-Healing Polymeric Gels.

This work demonstrates the successful application of dynamic covalent chemistry for the construction of self-healing gels from side-chain primary amine leucine pendant diblock copolymers of polyisobutylene (PIB) ((P(H2N-Leu-HEMA)-b-PIB)) in the presence of PIB based dialdehyde functionalized cross-linker (HOC-PIB-CHO) through imine (-HC═N-) bond formation without aiding any external stimuli. Gels were synthesized in 1,4-dioxane at room temperature at varied wt % of gelator concentration, [H2N]/[CHO] ratios and molecular weight of the block segments. The mechanical property of gels was examined by rheological measurements.

Structural characterization of telechelic polyisobutylene diol.

The chemical homogeneity of telechelic polyisobutylene diol (PIB-diol), prepared by hydroboration-oxidation of allyl telechelic PIB obtained by reacting living PIB with allyltrimethylsilane, was investigated by liquid chromatography at critical conditions (LCCC) and HPLC coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). A normal phase gradient HPLC method was developed that was able to separate the as-synthesized PIB-diol into three components; PIB-diol, PIB-monool and PIB without any OH functionality. These were analyzed by MALDI-TOF MS, which suggested that the reaction of living PIB with allyltrimethylsilane was incomplete.

Surface characterization and protein interactions of segmented polyisobutylene-based thermoplastic polyurethanes.

The surface properties and biocompatibility of a class of thermoplastic polyurethanes (TPUs) with applications in blood-contacting medical devices have been studied. Thin films of commercial TPUs and novel polyisobutylene (PIB)-poly(tetramethylene oxide) (PTMO) TPUs were characterized by contact angle measurements, X-ray photoelectron spectroscopy, and atomic force microscopy (AFM) imaging. PIB-PTMO TPU surfaces have significantly higher C/N ratios and lower amounts of oxygen than the theoretical bulk composition, which is attributed to surface enrichment of PIB.

Long term in vitro biostability of segmented polyisobutylene-based thermoplastic polyurethanes.

Long term in vitro biostability of thermoplastic polyurethanes (TPUs) containing mixed polyisobutylene (PIB)/poly(tetramethylene oxide) (PTMO) soft segment was studied under accelerated conditions in 20% H(2)O(2) solution containing 0.1M CoCl(2) at 50 °C to predict resistance to metal ion oxidative degradation (MIO) in vivo. The PIB-based TPUs showed significant oxidative stability as compared to the commercial controls Pellethane 2363-55D and 2363-80A.

Peptide surface modification of P(HEMA-co-MMA)-b-PIB-b-P(HEMA-co-MMA) block copolymers.

Peptide surface modification of poly[(methyl methacrylate-co-hydroxyethyl methacrylate)-b-isobutylene-b-(methyl methacrylate-co-hydroxyethyl methacrylate)] P(MMA-co-HEMA)-b-PIB-b-P(MMA-co-HEMA) triblock copolymers with different HEMA/MMA ratios has been accomplished using an efficient synthetic procedure. The triblock copolymers were reacted with 4-fluorobenzenesulfonyl chloride (fosyl chloride) in pyridine to obtain the activated polymers [poly{(methyl methacrylate-co-fosyloxyethyl methacrylate)-b-isobutylene-b-(methyl methacrylate-co-fosyloxyethyl methacrylate)}] P(MMA-co-FEMA)-b-PIB-b-P(MMA-co-FEMA), with an activating efficiency of 80-90%. The resulting polymers were soluble in chloroform, and their solutions were used to coat thin uniform films with a predetermined thickness on smooth steel surfaces.

In vivo and in vitro characterization of poly(styrene-b-isobutylene-b-styrene) copolymer stent coatings for biostability, vascular compatibility and mechanical integrity.

The TAXUS Express 2 Paclitaxel Eluting Coronary Stent System employs a coating consisting of the thermoplastic elastomer, poly(styrene-b-isobutylene-b-styrene; SIBS), selected for its drug-eluting characteristics, vascular compatibility, mechanical properties, and biostability. This study was conducted to evaluate the impact of different SIBS (17-51 mole % styrene) compositions on mechanical properties, chemical stability, and vascular compatibility. Mechanical property (stress-strain measurements) and stability studies were conducted on polymer films with five different styrene contents (17, 24, 32, 39, and 51 mole %).

Synthesis, characterization, properties, and drug release of poly(alkyl methacrylate-b-isobutylene-b-alkyl methacrylate).

Polyisobutylene (PIB)-based block copolymers have attracted significant interest as biomaterials. Poly(styrene-b-isobutylene-b-styrene) (SIBS) has been shown to be vascularly compatible and, when loaded with paclitaxel (PTx) and coated on a coronary stent, has the ability to deliver the drug directly to arterial walls. Modulation of drug release from this polymer has been achieved by varying the drug/polymer ratio, by blending SIBS with other polymers, and by derivatizing the styrene end blocks to vary the hydrophilicity of the copolymer.

Controlled delivery of paclitaxel from stent coatings using poly(hydroxystyrene-b-isobutylene-b-hydroxystyrene) and its acetylated derivative.

A poly(styrene-b-isobutylene-b-styrene) (SIBS) triblock polymer is employed as the polymer drug carrier for the TAXUS Express2 Paclitaxel-Eluting Coronary Stent system (Boston Scientific Corp.). It has been shown that the release of paclitaxel (PTx) from SIBS can be modulated by modification of either drug-loading ratio or altering the triblock morphology by blending.

Simple synthesis of a weak nucleophilic base (4-ethyl-2,6-diisopropyl-3,5-dimethylpyridine) evidencing a double Janus group effect.

By analogy with 2,6-di-tert-butylpyridine and its 4-methyl-substituted derivatives, which are nonnucleophilic bases, 4-ethyl-2,6-diisopropyl-3,5-dimethylpyridine (4) is also such a base. The isopropyl groups (Janus-like groups) are forced by the neighboring methyl groups to turn their "tert-butyl-analogue face" toward the heteroatom, thereby protecting it sterically against electrophilic attack. The synthesis proceeds in two stages via the corresponding pyrylium salt 3 that is obtained by alkene diacylation.