No abstract

Alcohol-induced hangover, defined by a series of symptoms, is the most commonly reported consequence of excessive alcohol consumption. Alcohol hangovers contribute to workplace absenteeism, impaired job performance, reduced productivity, poor academic achievement, and may compromise potentially dangerous daily activities such as driving a car or operating heavy machinery. These socioeconomic consequences and health risks of alcohol hangover are much higher when compared to various common diseases and other health risk factors. Nevertheless, unlike alcohol intoxication the hangover has received very little scientific attention and studies have often yielded inconclusive results. Systematic research is important to increase our knowledge on alcohol hangover and its consequences. This consensus paper of the Alcohol Hangover Research Group discusses methodological issues that should be taken into account when performing future alcohol hangover research. Future research should aim to (1) further determine the pathology of alcohol hangover, (2) examine the role of genetics, (3) determine the economic costs of alcohol hangover, (4) examine sex and age differences, (5) develop common research tools and methodologies to study hangover effects, (6) focus on factor that aggravate hangover severity (e.g., congeners), and (7) develop effective hangover remedies.

Research on human subjects analyzing blood and urine samples determined biological correlates that may explain the pathology of alcohol hangover. These analyses showed that concentrations of various hormones, electrolytes, free fatty acids, triglycerides, lactate, ketone bodies, cortisol, and glucose were not significantly correlated with reported alcohol hangover severity. Also, markers of dehydration (e.g., vasopressin) were not significantly related to hangover severity. Some studies report a significant correlation between blood acetaldehyde concentration and hangover severity, but most convincing is the significant relationship between immune factors and hangover severity. The latter is supported by studies showing that hangover severity may be reduced by inhibitors of prostaglandin synthesis. Several factors do not cause alcohol hangover but can aggravate its severity. These include sleep deprivation, smoking, congeners, health status, genetics and individual differences. Future studies should more rigorously study these factors as well as biological correlates to further elucidate the pathology of alcohol hangover.

No abstract

An injectable thermosensitive hydrogel to promote local and sustained release of small nanosized (10–20 nm) siRNA polyplexes.

This review focusses on the rational design of materials (from polymers to hydrogel materials) to achieve successful local delivery of therapeutic nucleic acids.

For the design of new polymeric-based drug delivery systems, understanding how multiple functionalities in the polymer structure are influencing each other in particle formation is important. Therefore in this study, the balance between hydrophobic and electrostatic interactions has been investigated for thermosensitive plasmid DNA (pDNA)-loaded polyplexes. NPD triblock copolymers consisting of a thermosensitive poly(N-isopropylacrylamide) (PNIPAM, N), a hydrophilic poly(ethylene glycol) (PEG, P) and a cationic poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA, D) block with different block lengths were prepared using a hetero-functional PEG macroinitiator. Cloud points of the thermosensitive polymers in HBS buffer (20 mM HEPES, 150 mM NaCl, pH 7.4) were determined by light scattering and ranged between 33 °C and 34 °C for the different polymers. The binding and condensation properties of these thermosensitive polymers and pDNA were studied taking non-thermosensitive PD polymers as controls. The size, surface charge, and stability of the formed colloidal particles (‘polyplexes’) were studied as a function of polymer block lengths, N/P charge ratio, and temperature. The NPD polymers were able to self-assemble into polyplex nanostructures with hydrodynamic sizes ranging between 150 and 205 nm at room temperature in HBS buffer as determined by dynamic light scattering. Polyplexes prepared with a low N/P charge ratio of 1 aggregated upon heating to 37 °C, which was not observed at higher N/P charge ratios. When the length of the cationic D block was relatively long compared to the thermosensitive N block, stable polyplexes were formed at all N/P ratios and elevated temperatures. 1H-NMR studies, static light scattering and ζ-potential measurements further supported the stability of these polyplexes at 37 °C. Finally, the presence of thermosensitive blocks in NPD-based polyplexes resulted in better cytocompatibility compared to PD-based polyplexes with similar efficiencies of delivering its cargo into HeLa cells.

ABC triblock copolymers with a poly(ethylene glycol) (PEG) midblock have attractive properties for biomedical applications because of PEG’s favorable properties regarding biocompatibility and hydrophilicity. However, easy strategies to synthesize polymers containing a PEG midblock are limited. In this study, the successful synthesis of a heterofunctional PEG macroinitiator containing both an azoinitiator and an atom transfer radical polymerization (ATRP) initiator is demonstrated. This novel PEG macroinitiator allows the development of elegant synthesis routes for PEG midblock-containing ABC copolymers that does not require protection of initiating sites or polymer end-group postmodification. Polymers with outer blocks composed of different monomers were synthesized to illustrate the versatility of this macroinitiator. N-Isopropylacrylamide (NIPAM) was included to obtain thermosensitive polymers, 2-(dimethylamino)ethyl methacrylate (DMAEMA) provided pH-sensitive properties, and 2-hydroxyethyl acrylate (HEA) functioned as a noncharged hydrophilic block that also allows for postmodifications reactions. This synthesis approach can further contribute to the design of high-precision polymers with tailorable block compositions and polymer topologies, which is highly attractive for applications in nanotechnology.