Chlorzoxazone, an SK-type potassium channel activator used in humans, reduces excessive alcohol intake in rats

Background Alcoholism imposes a tremendous social and economic burden. There are relatively few pharmacological treatments for alcoholism, with only moderate efficacy, and there is considerable interest in identifying additional therapeutic options. Alcohol exposure alters SK-type potassium channel (SK) function in limbic brain regions. Thus, positive SK modulators such as chlorzoxazone (CZX), a US Food and Drug Administration–approved centrally acting myorelaxant, might enhance SK function and decrease neuronal activity, resulting in reduced alcohol intake. Methods We examined whether CZX reduced alcohol consumption under two-bottle choice (20% alcohol and water) in rats with intermittent access to alcohol (IAA) or continuous access to alcohol (CAA). In addition, we used ex vivo electrophysiology to determine whether SK inhibition and activation can alter firing of nucleus accumbens (NAcb) core medium spiny neurons. Results Chlorzoxazone significantly and dose-dependently decreased alcohol but not water intake in IAA rats, with no effects in CAA rats. Chlorzoxazone also reduced alcohol preference in IAA but not CAA rats and reduced the tendency for rapid initial alcohol consumption in IAA rats. Chlorzoxazone reduction of IAA drinking was not explained by locomotor effects. Finally, NAcb core neurons ex vivo showed enhanced firing, reduced SK regulation of firing, and greater CZX inhibition of firing in IAA versus CAA rats. Conclusions The potent CZX-induced reduction of excessive IAA alcohol intake, with no effect on the more moderate intake in CAA rats, might reflect the greater CZX reduction in IAA NAcb core firing observed ex vivo. Thus, CZX could represent a novel and immediately accessible pharmacotherapeutic intervention for human alcoholism. Key Words: Alcohol intake; intermittent; neuro-adaptation; nucleus accumbens; SK potassium channel

Manufacturing practices and performances: A Malaysian study

The purpose of this study is to identify the most common manufacturing practices adopted by the Malaysian manufacturers, company performance factors and relationship between practices and performances. To fulfil the study objectives, 400 manufacturers were surveyed by a standard 400 questionnaire. Three research methodologies such as descriptive analysis, ANOVA and regression analysis have been employed in this study. The analysis revealed that Malaysian manufacturers focus on optimizing three critical performance factors: product development, less customer return rate and on time delivery (OTD). The most important competitive factor was found to be company reputation and design and manufacturing capacity is the least important factor. The findings also proved that manufacturing practices significantly influence company performances

Manufacturing Yield Improvement by Clustering

Dealing with product yield and quality in manufacturing industries is getting more difficult due to the increasing volume and complexity of data and quicker time to market expectations. Data mining offers tools for quick discovery of relationships, patterns and knowledge in large databases. Growing self-organizing map (GSOM) is established as an efficient unsupervised datamining algorithm. In this study some modifications to the original GSOM are proposed for manufacturing yield improvement by clustering. These modifications include introduction of a clustering quality measure to evaluate the performance of the programme in separating good and faulty products and a filtering index to reduce noise from the dataset. Results show that the proposed method is able to effectively differentiate good and faulty products. It will help engineers construct the knowledge base to predict product quality automatically from collected data and provide insights for yield improvement.