There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Electrospinning: a fascinating fiber fabrication technique.

Size-Distribution Analysis of Macromolecules by Sedimentation Velocity Ultracentrifugation and Lamm Equation Modeling

Block copolymer micelles for drug delivery: design, characterization and biological significance

The rapid recognition of intravenously injected colloidal carriers, such as liposomes and polymeric nanospheres from the blood by Kupffer cells, has initiated a surge of development for "Kupffer cell-evading" or long-circulating particles. Such carriers have applications in vascular drug delivery and release, site-specific targeting (passive as well as active targeting), as well as transfusion medicine. In this article we have critically reviewed and assessed the rational approaches in the design as well as the biological performance of such constructs. For engineering and design of long-circulating carriers, we have taken a lead from nature. Here, we have explored the surface mechanisms, which affords red blood cells long-circulatory lives and the ability of specific microorganisms to evade macrophage recognition. Our analysis is then centered where such strategies have been translated and fabricated to design a wide range of particulate carriers (e.g., nanospheres, liposomes, micelles, oil-in-water emulsions) with prolonged circulation and/or target specificity. With regard to the targeting issues, attention is particularly focused on the importance of physiological barriers and disease states.

Long-Circulating and Target-Specific Nanoparticles: Theory to Practice

Part I: Instrumentation Part II: Equilibrium Methods Part III: Transport Methods Part IV: Specific Applications to Biochemical and Polymer Systems

Analytical ultracentrifugation in biochemistry and polymer science

The intrinsic viscosity of biological macromolecules. Progress in measurement, interpretation and application to structure in dilute solution.

Rationale: Intermittent footshock stress reliably reinstates extinguished alcohol-taking behavior in drug-free rats, but the neurochemical events involved in this effect are not known. Objective: We studied here whether two main modulators of stress responses, corticotropin-releasing factor (CRF) and corticosterone, are involved in reinstatement of alcohol seeking induced by the intermittent footshock stressor. Methods: Rats were given alcohol in a two-bottle choice procedure (water versus alcohol) for 30 days and were then trained for 60 min per day to press a lever for alcohol (12% w/v) for 24–30 days in operant conditioning chambers. After stable drug-taking behavior was obtained, lever pressing for alcohol was extinguished by terminating drug delivery for 5–8 days. Reinstatement of alcohol seeking was then determined after exposure to intermittent footshock (0.8 mA; 10 min) in different groups of rats that were pretreated with CRF receptor antagonists or underwent adrenalectomy (ADX) to remove endogenous corticosterone from the body. Results: The CRF receptor antagonists, d-phe-CRF (0.3 or 1.0 µg; ICV) and CP-154,526 (15, 30 or 45 mg/kg; IP) attenuated footshock-induced reinstatement of alcohol seeking in a dose dependent manner. In contrast, the removal of circulating corticosterone by ADX had no effect on footshock stress-induced reinstatement of alcohol-taking behavior. In addition, the prevention of the footshock-induced rise in corticosterone while maintaining basal levels of the hormone by providing adrenalectomized rats with corticosterone pellets (50 mg/kg per day), had no effect on stress-induced reinstatement. Conclusions: These data suggest that CRF contributes to stress-induced relapse to alcohol seeking via its actions on extra-hypothalamic sites. The present data, and previous data with heroin- and cocaine-trained rats, point to a general role of CRF in relapse to drugs induced by stressors.

The role of corticotrophin-releasing factor in stress-induced relapse to alcohol-seeking behavior in rats

Copolymers of polylactide and poly(ethylene glycol) (PLA−PEG), which self-disperse in water to form spherical nonionic micelles, have been investigated as a novel biodegradable drug delivery system These copolymers are defined by the molecular weight ratios of their polylactide to poly(ethylene glycol) components (15:2 PLA−PEG and 2:5 PLA−PEG) and gave two peaks when purified by gel permeation chromatography (GPC) The first peak consisted of spherical micelles with a diameter of 156 nm for 15:2 PLA−PEG, and 189 nm for 2:5 PLA−PEG micelles after analysis by dynamic light scattering (DLS) and by transmission electron microscopy (TEM) The second peak was a PLA-depleted species resulting from the synthesis and did not form micelles Testosterone and sudan black B (SBB), which have different hydrophobicities, were used as “model drugs” to evaluate the drug loading ability of the micelles Ultracentrifugation sedimentation velocity studies confirmed that solubilization of the model drugs had occurred by 

Polylactide−Poly(ethylene glycol) Copolymers as Drug Delivery Systems. 1. Characterization of Water Dispersible Micelle-Forming Systems

Alpha-2 adrenoceptors are known to be involved in stress-induced reinstatement of heroin and cocaine seeking in laboratory animals. Here, we studied the involvement of these receptors in stress-induced reinstatement of alcohol seeking by using an agonist (lofexidine) and an antagonist (yohimbine) of these receptors, which inhibit and activate, respectively, noradrenaline transmission. We also tested the effect of lofexidine and yohimbine on alcohol self-administration. Lofexidine is used clinically for treating opiate withdrawal symptoms and yohimbine induces stress-like responses in humans and non-humans. Rats were trained to self-administer alcohol (12% w/v, 1 h/day) and after extinction of the alcohol-reinforced behavior, they were tested for the effect of lofexidine (0, 0.05 and 0.1 mg/kg, IP) on reinstatement of alcohol seeking induced by intermittent footshock stress (10 min, 0.8 mA) or for the effect of yohimbine (0, 1.25 and 2.5 mg/kg, IP) on reinstatement of alcohol seeking. Other rats were trained to self-administer alcohol, and after stable responding, the effects of lofexidine and yohimbine on alcohol self-administration were determined. Pretreatment with lofexidine (0.05 mg/kg and 0.1 mg/kg) attenuated stress-induced reinstatement of alcohol seeking and also decreased alcohol self-administration. In contrast, yohimbine pretreatment potently reinstated alcohol seeking after extinction and also induced a profound increase in alcohol self-administration. Results indicate that activation of alpha-2 adrencoceptors is involved in both stress-induced reinstatement of alcohol seeking and alcohol self-administration. To the degree that the present results are relevant to human alcoholism, alpha-2 adrencoceptor agonists should be considered in the treatment of alcohol dependence.

Stephen E. Harding

Papers

Analytical ultracentrifugation in biochemistry and polymer science

The intrinsic viscosity of biological macromolecules. Progress in measurement, interpretation and application to structure in dilute solution.

The role of corticotrophin-releasing factor in stress-induced relapse to alcohol-seeking behavior in rats

Polylactide−Poly(ethylene glycol) Copolymers as Drug Delivery Systems. 1. Characterization of Water Dispersible Micelle-Forming Systems

Role of alpha-2 adrenoceptors in stress-induced reinstatement of alcohol seeking and alcohol self-administration in rats.