Overexpression of Aldose Reductase Render Mouse Hepatocytes More Sensitive to Acetaminophen Induced Oxidative Stress and Cell Death

Acetaminophen (APAP) a commonly used drug for decrease the fever and pain but is capable to induced hepatotoxicity at over dose. This study was carried out to investigate the effect of APAP on the expression of anti-apoptotic and antioxidative defense genes, and whether aldose reductase over-expressing plasmid capable to protect against APAP-induced oxidative stress and cell death. APAP treatment induced oxidative stress and hepatotoxicity, and significantly increased aldose reductase mRNA and protein expression in mouse hepatocyte (AML-12). Unexpectedly, AML-12 cells over-expressing aldose reductase augmented APAP-induced reduction in cell viability, reactive oxygen species (ROS) production, glutathione (GSH) depletion and glutathione S-transferase A2 expression. Moreover, over-expression of aldose reductase potentiated APAP induced reduction on proliferating cell nuclear antigen, B cell lymphoma-extra large (bcl-x_L), catalase, glutathione peroxidase-1 (GPx-1) and abolished APAP-induced B-cell lymphoma 2 (bcl-2) inductions. Further, over-expression of aldose reductase significantly abolished AMP activated protein kinase (AMPK) activity in APAP-treated cells and induced p53 expression. This results demonstrate that APAP induced toxicity in AML-12, increased aldose reductase expression, and over-expression of aldose reductase render this cell more susceptible to APAP induced oxidative stress and cell death, this probably due to inhibition AMPK or bcl-2 activity, or may due to competition between aldose reductase and glutathione reductase for NADPH.     

Age related changes in lipid peroxidation and antioxidants in elderly people

Advanced age is associated with an accumulation of free radical damage, which leads to physiological and clinical modifications. Age related changes resulting from free radical reactions include increasing levels of lipid peroxides, alterations in enzyme activities and greater osmotic fragility. The present study was conducted to estimate the level of lipid peroxidation product-Malondialdehyde and antioxidants Catalase and Glutathione in elderly people. An increase in lipid peroxidation and decrease in antioxidants was observed in normal elderly people. Highly significant increase in MDA and decrease in antioxidants was observed in elderly people when complicated with diabetes and hypertension. Supplementation of antioxidants may prevent further oxidative injury in elderly people.     

The timekeeping of Egyptian outflow clocks

Simple as the outflow clock principle may seem for the measurement of time, its translation into an accurate clock raises formidable technical and conceptual problems. An attempt is made here to reconstruct the Egyptians' consciousness of these problems, and the success of their solutions.     

Innovation in a federal state

As a country with a relatively small international reputation for manufacturing and, apparently, with an even smaller one for technology-based product and process innovation in manufacturing, Canada has a long way to go to develop its manufacturing and innovative activities to the stage reached by most European countries. Recently, however, a number of science and research policy studies have been made to examine problems associated with innovation in manufacturing. This present paper deals with two important elements associated with these studies, namely, the organization of the public sector in Canada and the roles and responsibilities of the public sector agencies with regard to the encouragement of technology-based innovation in manufacturing. As pointed out in the paper, the federal structure and the agencies within it may at present frustrate as well as encourage innovation. However, assuming that the appropriate policy objectives can be articulated and accepted, the removal of the principal public sector frustrations will be dependent upon better divisions of responsibility and labour between the three levels of government.     

Automation in textile machinery

During the period 1952 to 1965, there were strenuous world-wide efforts to produce an automated cotton spinning mill. These attempts, which involved the use of concepts developed outside the textile machinery industry (i.e. automatic transfer systems), were motivated by the need to reduce the very great amount of manual handling of packages between successive operations in the yarn manufacturing process.The case is unusual in that, while many of the developments were ‘technically successful’ in that installations were made which functioned satisfactorily in the mill), they were, without exception, commercially unsuccessful from the point of view of the machinery manufacturer and mill operator. This paper describes the economic forces which led to the attempts at automation, and explains why, after an expenditure in excess of £ 25 mill/on worldwide, commercial success was not achieved.The prime reason for failure lay in minor and major developments of existing individual machines, which had continued independently of automation research, and which had, to a great extent, obviated the economic need for automation. The surprising thing (in retrospect at least), is that, as production rates were increased step by step, development engineers working to produce automated systems saw, in the increasing speeds, only a challenge to their ingenuity — not a disappearance of the need for automatic transfer devices.A secondary reason for failure in the particular case of the Shirley Institute's automated card room sequence lay in the fact that the research was directed by a committee whose terms of reference were limited to pursuance of a defined goal — the development of an automated card room. The committee had no mandate to question the soundness of its objectives, and the work continued until a technically successful system was finally produced.     

Ultrasonic delay lines

This paper deals with the experimental aspects of ultrasonic delay lines in liquid media and is a sequel to a previous paper treating the general theory of such devices.Delay devices employing ultrasonic propagation through liquids have proved satisfactory for delay times of the order of 3 milliseconds or less. Such devices can be made broadband and give excellent reproduction of pulse shape. The design considerations for such devices are discussed and illustrated by actual examples.     

Query processing in a retrospective document retrieval system that uses word fragments as language elements

The structure of a retrospective information retrieval system that uses equifrequent word or text fragments is described, and its advantages over word oriented systems are mentioned briefly. Word fragments are proposed as retrieval elements, and a discussion is given of the changes required in order to process a query. Some necessary modifications in the treatment of logical operators are described, and two conditions are postulated as necessary for the successful operation of the system. Aspects of query processing are illustrated by experimental results obtained from single and two-term queries applied to a portion of the MARC tapes.     

The treatment of uncertainty in the sciences

For some 300 years the modelling of uncertainty in the sciences has been totally dominated by probabilistic methods. Now, following major criticism of the theoretical foundations of probability theory, other approaches to dealing with uncertainty are being explored.     

An experimental study evaluating professional development activities within a state funded pre-kindergarten program

This paper describes the implementation and evaluation for scaling up a comprehensive early childhood teacher professional development program into 11 communities across 2 years with funding through state legislative actions. The comprehensive program had four major components based on results from a previous multi-condition random assignment study across four states. The previous results demonstrated that the most optimum approach for supporting children??s school readiness included: (1) teacher on-line professional development with facilitation, (2) classroom mentoring, (3) implementation of a research-based curriculum, and (4) technology-driven progress monitoring that informed instruction. The comprehensive professional development program was evaluated in a new state program designed to bring childcare, Head Start, and public school pre-kindergarten together into integrated partnerships. In Year 1, 220 teachers serving 3834 children were randomly assigned to either receive the comprehensive program or not. Teachers who served as controls in Year 1 received the program in Year 2, and those who received the program in Year 1 participated for an additional year in Year 2, allowing for examination of the effects of one versus 2 years of participation. The program improved teachers instructional practices relative to controls, and a second year of participation resulted in greater gains in children??s language and literacy. Results support the need for well-integrated, comprehensive professional development for early childhood educators.