Rapid induction of Pavlovian approach to an ethanol-paired visual cue in mice

Rationale Although many studies have shown Pavlovian conditioned approach to cues paired with natural reinforcers, it has been quite difficult to induce such behavior with drug reinforcers. Objectives This experiment tested a novel Pavlovian procedure for inducing approach to a conditioned stimulus (CS) paired with ethanol. Methods Mice (NZB/B1NJ, DBA/2J) received intraperitoneal injections of ethanol (2 g/kg) immediately before 10-min exposure to a rectangular chamber that contained a distinctive visual cue (star) at one end (Paired group, CS+ trials). On alternate days, saline injection preceded apparatus exposure with no distinctive cues (CS− trials). Unpaired control mice received ethanol in the home cage 60–75 min after each CS+ trial. Results NZB/B1NJ Paired group mice spent increasing amounts of time (>85% of the session) in proximity to the star, whereas Unpaired group mice did not. DBA/2J Paired group mice spent slightly more time on the star side than Unpaired group mice but did not show an acquisition curve. Postconditioning tests showed a strong preference for the star side in Paired groups from both strains after saline injection. However, only NZB/B1NJ mice showed a preference after ethanol. Conclusions This study provides the first unambiguous demonstration of Pavlovian conditioned approach to an ethanol-paired visual stimulus in the absence of any contingency between the animal’s behavior and drug exposure. This effect, which is remarkable both in terms of its magnitude and the rapidity with which it was produced (within 2–3 trials), may be related to the cue-associated craving that accompanies alcohol and drug addiction.     

Normal cognitive behavior in two distinct congenic lines of transgenic mice hyperexpressing mutant APP SWE

Amyloid deposition appears to be an early and crucial event in Alzheimer's disease (AD). To generate animal models of AD, mice expressing full-length amyloid precursor protein (APP), with mutations linked to FAD, have been created. These animals exhibit abnormalities characteristic of AD, including deposits of beta-amyloid (Abeta), neuritic plaques, and glial responses. In studies of cognition in these animals, there have been several reports of memory disturbances well before the appearance of amyloid deposits. We have developed two distinct lines of transgenic mice (C3-3 and E1-2) that express the "Swedish" variant of APP (APP(SWE)) at levels that are approximately three-fold higher than endogenous mouse APP. Both lines have been backcrossed to C57BL/6J mice for 10 generations. Here, we use longitudinal and cross-sectional studies to evaluate the cognitive performance of our animals, where the concentration of Abeta1-42 in brain increases with aging from low levels (2-10 pmol/g) at 6-14 months of age to relatively high levels (60-100 pmol/g) at 24-26 months, when deposits of Abeta were beginning to form. When 12-month-old mice were tested in tasks that assess reference and working memory, transgenic mice from both lines could not be distinguished from nontransgenic littermates. Further study of 24- to 26-month-old transgenic mice (C3-3 line) found no evidence of memory impairment despite the presence of high levels of human Abeta (60-100 pmol/g). Thus, the expression of APP(SWE) at approximately three-fold over endogenous levels, which is sufficient to induce amyloid deposition at advanced ages, does not significantly erode cognitive performance in aged mice.     

Intralesional bleomycin sulfate in treatment of recalcitrant warts

There has long been a pressing need for an effective, easy, and safe treatment for recalcitrant warts. Intralesional injection of bleomycin promises to meet these criteria most nearly. The bleomycins, a group of sulfur-containing polypeptide compounds, were isolated from Streptomyces verticillus, a Japanese soil fungus, by Umezawa¹ in 1962. They have both antibiotic and cytotoxic properties. The cytotoxic effect depends on the ability to cause DNA strand scission, especially in dividing cells entering the mitotic phase.² It affects both DNA and protein synthesis as well as cell division.

Bleomycin is a broad-spectrum antibiotic with a variable antibacterial activity. Umezawa³ demonstrated that bleomycin also inactivated SV40 by scission of both strands of its DNA. It is possible, therefore, that it could act directly on human papillomavirus (HPV) in the same way.     

Iterating ‘addiction’: Residential relocation and the spatio-temporal production of alcohol and other drug consumption patterns

Addiction is generally understood to be characterised by a persistent pattern of regular, heavy alcohol and other drug consumption. Current models of addiction tend to locate the causes of these patterns within the body or brain of the individual, sidelining relational and contextual factors. Where space and place are acknowledged as key factors contributing to consumption, they tend to be conceived of as static or fixed, which limits their ability to account for the fluid production and modulation of consumption patterns over time. In this article we query individualised and decontextualised understandings of the causes of consumption patterns through an analysis of accounts of residential relocation from interviews undertaken for a large research project on experiences of addiction in Australia. In conducting our analysis we conceptualise alcohol and other drug consumption patterns using Karen Barad’s notions of intra-action and spatio-temporality, which allow for greater attention to be paid to the spatial and temporal dimensions of the material and social processes involved in generating consumption patterns. Drawing on 60 in-depth interviews conducted with people who self-identified as experiencing an alcohol and other drug addiction, dependence or habit, our analysis focuses on the ways in which participant accounts of moving enacted space and time as significant factors in how patterns of consumption were generated, disrupted and maintained. Our analysis explores how consumption patterns arose within highly localised relations, demonstrating the need for understandings of consumption patterns that acknowledge the indivisibility of space and time in their production. In concluding, we argue for a move away from static conceptions of place towards a more dynamic conception of spatio-temporality, and suggest the need to consider avenues for more effectively integrating place and time into strategies for generating preferred consumption patterns and initiating and sustaining change where desired.     

Causes of the decrease in cardiovascular mortality

In the last 15 years there has been a dramatic, unprecedented decrease in the mortality rate from cardiovascular disease in the United States, especially from coronary heart disease and stroke. Possible causes of the decline in the coronary heart disease mortality rate include the development of the concept of acute coronary care, new drugs, sophisticated surgical techniques such as coronary artery bypass, noninvasive diagnostic methods for earlier disease detection, and the identification of specific cardiovascular risk factors. The decrease has been temporarily related to increased risk factor awareness and modification (cigarette smoking cessation, hypertension control, diet change and reduction in cholesterol). Thus, both primary prevention through lifestyle changes and improved treatment regimens have played a role in the decline. Recent studies showing the benefit of cholesterol reduction emphasize the potential for even greater decreases.     

Clotrimazole treatment of oral candidiasis in patients with neoplastic disease

A double-blind controlled study was performed to evaluate the effectiveness of Clotrimazole in the treatment of oral candidiasis in patients with neoplastic disease. Six of seven patients who received clotrimazole had resolution of symptoms and signs of oral candidiasis. In five of six patients who received placebo, clinical progression of signs and symptoms occurred, esophagitis developed, and amphotericin B therapy had to be given. No toxicity was observed that could be attributed to clotrimazole. The results were statistically significant (p = 0.025 by Fisher's exact test). Clotrimazole is effective therapy for oral candidiasis in patients with neoplastic disease, and may prevent the development of esophagitis.