Substance Abuse Therapeutics

This chapter provides a broad overview of therapies for substance abuse. These therapies are understood in the context of the history of drug use in the United States and factors that influenced the expansion and regulation of substance use. This is followed by a discussion of how the complexity of these factors was associated with difficulties in understanding substance misuse and created challenges to the creation of effective treatment systems. The chapter reviews the moral and disease models of addiction before discussing the diagnosis of substance-related disorders. The chapter describes major treatment approaches and their efficacy

An improved fungal mounting technique for Nomarski microscopy

The 'sellotape technique' of Butler and Mann (1959) with lactophenol cotton blue stain is widely used in these laboratories for the production of non-permanent fungal mounts for class examination using bright field microscopy. The technique allows very little disturbance of fungal structure for identification and taxonomic work. The major drawbacks of this technique for permanent mounts are the fact that the tape itself is not inert and the adhesive reacts with the lactophenol forming droplets which cover the field of view (Onions et al., l98l). The stressed nature of the tape also gives rise to problems due to interference patterns during Nomarski microscopy. The increasing use of diflerential interference contrast(Nomarski) microscopy in mycological studies prompted a re-evaluation of techniques used in the preparation of fungal mounts. Other types of nonstressed tapes were found but these proved not to be sticky enough to pick up fungal structures from agar media cleanly and without undue damage. The technique described below uses a silicone based adhesive in conjunction with the slightly modified polyvinyl alcohol mountant of Salmon (1954), updated by Omar et al. (1918), and represents a modification and improvement of the technique described by Bretz and Berry (1964)

Kinetics of reduction of a Resazurin-based photocatalytic activity ink

The kinetics of reduction of a Resazurin, Rz,-based photocatalyst activity indicator ink, paii, on a commercial sample of self-cleaning glass, Activ™ is examined; the latter has ca. a 15nm compact coating of anatase TiO2 which serves as the active photocatalyst layer. The rate of dye reduction is reduced significantly by the presence of ambient O2. In the absence of O2, the measured change in film absorbance due to Rz, d Δ Abs/dt, was found to be independent of both [Rz] and film thickness, b. It is shown that this translates to the rate of dye reduction, d[Rz]/dt, being independent of the concentration of the Rz in the ink film, [Rz], and inversely proportional to film thickness, b. The observed kinetics are rationalised in terms of a kinetic model in which the rate determining step is the reduction of photocatalyst surface-adsorbed Rz by photo-generated surface electrons, with all photocatalyst surface sites occupied by Rz. Further work suggests that, if the kinetics of the photocatalysed reduction of the Rz paii were diffusion-controlled, then the decay in [Rz] would be first order and dependent upon b-2

NMR analysis of Nile Blue (C. I. Basic Blue 12) and Thionine (C. I. 52000) in solution

The dyes Nile Blue (C. I. Basic Blue 12, NB) and Thionine (C. I. 52000, TH) were examined in both ionic and neutral forms in different solvents using NMR and UV-visible Spectroscopy to firmly establish the structures of the molecules and to assess the nature and extent of their aggregating characteristics. 1H and 13C NMR assignments and chemical shift data were used along with (for NB) nuclear Overhauser effect information enabling a structure for self-assembly to be proposed. In both cases these data were supplemented with variable temperature, dilution and diffusion-based experimental results using 1H NMR spectroscopy thereby enabling the extended aggregate structures to be assessed in terms of the relative strength of self-association and the extent to which extended aggregates could form. Full and detailed solution phase NMR analysis of such dyes, especially the two studied in this context, have either not been widely reported or have not been studied to the depth presented here. The data and their interpretation form an important addition to the analysis of this class of dye compounds and provide additional insight into the effects of self-assembly on the behaviour of such molecules in various solution-phase environments

Long-Period Giant Companions to Three Compact, Multiplanet Systems

Understanding the relationship between long-period giant planets and multiple smaller short-period planets is critical for formulating a complete picture of planet formation. This work characterizes three such systems. We present Kepler-65, a system with an eccentric (e = 0.28 ± 0.07) giant planet companion discovered via radial velocities (RVs) exterior to a compact, multiply transiting system of sub-Neptune planets. We also use precision RVs to improve mass and radius constraints on two other systems with similar architectures, Kepler-25 and Kepler-68. In Kepler-68 we propose a second exterior giant planet candidate. Finally, we consider the implications of these systems for planet formation models, particularly that the moderate eccentricity in Kepler-65\u27s exterior giant planet did not disrupt its inner system

The correlation of early flow disturbances with the development of infrainguinal graft stenosis: A 10-year study of 341 autogenous vein grafts

AbstractPurpose: Although duplex surveillance of infrainguinal bypass grafts is widely accepted, the optimal frequency and intensity of graft surveillance remains controversial. Earlier reports have suggested that grafts can be stratified into high-risk and low-risk groups based on the presence or absence of early graft flow disturbances. The purpose of this study was to provide long-term data in determining whether early graft flow disturbances detected by means of duplex scanning can predict the development of intrinsic vein graft stenosis. Methods: We reviewed a series of patients undergoing prospective duplex graft surveillance after autogenous infrainguinal bypass grafting procedures from 1987 to 1997. Patients included in the study underwent at least one duplex scan within 3 months of graft implantation and were observed for a minimum of 6 months. Grafts were categorized as abnormal when a focal flow disturbance with a peak systolic velocity greater than 150 cm/s was identified within 3 months of graft implantation. Results: Of 341 vein grafts in 296 patients who met inclusion criteria, 89 grafts (26%) required revision for intrinsic stenosis; the mean follow-up period was 35 months (range, 6 months to 10 years). Early flow disturbances were detected in 84 (25%) grafts. Grafts with early flow disturbances were more likely to ultimately require revision (43% vs 21%; P = .0001) and required initial revision earlier (8 months vs 16 months; P = .019). Eighty-two percent of initial graft revisions occurred in the first 2 postoperative years; 69% occurred in the first year. However, an annual 2% to 4% incidence of late-appearing graft stenosis persisted during long-term follow-up. An additional 24 patients (7% of grafts) required an inflow or outflow reconstruction. Conclusion: Grafts with early postoperative flow disturbances detected by means of duplex scanning have nearly three times the incidence of graft-threatening stenosis and an earlier requirement for revision, when compared with normal grafts. This suggests that the biology and etiology of these lesions may differ. These data support not only aggressive efforts to detect early graft lesions to stratify grafts at highest risk, but also continued lifelong graft surveillance to detect late-appearing lesions, inflow and outflow disease progression, and maximize graft patency. (J Vasc Surg 1999;30:8-15.

Characterization of an electron conduit between bacteria and the extracellular environment

A number of species of Gram-negative bacteria can use insoluble minerals of Fe(III) and Mn(IV) as extracellular respiratory electron acceptors. In some species of Shewanella, deca-heme electron transfer proteins lie at the extracellular face of the outer membrane (OM), where they can interact with insoluble substrates. To reduce extracellular substrates, these redox proteins must be charged by the inner membrane/periplasmic electron transfer system. Here, we present a spectro-potentiometric characterization of a trans-OM icosa-heme complex, MtrCAB, and demonstrate its capacity to move electrons across a lipid bilayer after incorporation into proteoliposomes. We also show that a stable MtrAB subcomplex can assemble in the absence of MtrC; an MtrBC subcomplex is not assembled in the absence of MtrA; and MtrA is only associated to the membrane in cells when MtrB is present. We propose a model for the modular organization of the MtrCAB complex in which MtrC is an extracellular element that mediates electron transfer to extracellular substrates and MtrB is a trans-OM spanning ß-barrel protein that serves as a sheath, within which MtrA and MtrC exchange electrons. We have identified the MtrAB module in a range of bacterial phyla, suggesting that it is widely used in electron exchange with the extracellular environment