Vitamin B1 blocks damage caused by hyperglycemia

Diabetes accelerates the aging process and leads to complications that include blindness, renal failure, nerve damage, stroke, and cardiovascular disease. It has been hypothesized that high plasma glucose concentrations are responsible for increased mitochondrial free radical production and subsequent inactivation of glyceraldehyde phosphate dehydrogenase (GAPDH) in vascular endothelial cells and other cells implicated in these complications. As a result of the decreased ability of GAPDH to process upstream metabolites, three pathways of metabolic damage are activated, which include the advanced glycation end-product formation pathway, the protein kinase C pathway, and the hexosamine pathway. All three pathways have been implicated in abnormal cell signaling in diabetes. A group of German and U.S. scientists has now found that treating diabetic rats with high doses of benfotiamine, a lipid-soluble form of vitamin B1, can prevent diabetic retinopathy and all three forms of metabolic damage by stimulating transketolase activity and thus diverting excess metabolites toward the pentose pathway. Although vitamin B1 is available over the counter, the researchers at this time do not advocate self-treatment without further clinical data.     

Does the road to muscle rejuvenation go through Notch?

The capacity of skeletal muscles to repair and regenerate declines during aging in humans, and this decline may lead to muscle loss and frailty. Conboy et al. show that injured muscles of aging mice are defective in Notch signaling, because up-regulation of the Notch ligand, Delta-1, is impaired. Delta-1 promotes proliferation of the satellite cells that repair damaged muscles, and Conboy et al. show that experimental activation of Notch signaling is sufficient to reverse the age-related decline in muscle regenerative capacity. Extension of these important findings to humans could lead to the development of new therapeutic approaches to maintain muscle function during aging.     

Creating new neurons in old brains

The brains of aged rodents exhibit decreased neurogenesis as compared to those of young adult rodents. Basal neurogenesis has previously been shown to increase in the young adult rodent brain upon the administration of growth factors. However, it is unknown whether similar treatment can affect this process in the aging brain. A recent paper published in the June 2003 issue of the journal Aging Cell reveals that two growth factors can stimulate neurogenesis in aged mice. This result raises the possibility that similar treatments may be used in humans to help maintain normal brain function in old age.     

Human resource practices of multinational organizations in Belgium

This study uses data from a survey of 117 large organizations located in Belgium to examine the relationship between corporate ownership and personnel practices. Results obtained from multivariate analyses supported the general hypothesis that personnel policies and practices vary as a function of ownership and nationality. For example, foreign-owned firms are found to be more advanced in their adoption of methods to gain employee loyalty and commitment than domestic enterprises. In addition to ownership effects, the moderating effects of some key organizational characteristics were examined. This shows that large differences exist with respect to the human resource practices used in firms as a function of management philosophy, creative strategy and industry sector.     

Environmental Tobacco Smoke: Exposure-Response Relationships in Epidemiologic Studies

Demonstration of a dose-response relationship for environmental tobacco smoke (ETS) is an important indication of causality. Central to the analysis and interpretation of dose-response relations as described in epidemiological studies is the relationship between dose and exposure. It must be recognized that in studies of ETS we have only surrogate measures of dose, and these surrogate measures (based on exposure) are imperfect. The question-based measures of ETS exposure generally have not been standardized, may have limited validity and reliability, and cannot comprehensively describe total ETS exposure, exposure to individual ETS components, nor doses of biologically relevant agents at target sites. Nevertheless, useful data have been yielded in epidemiologic studies linking ETS exposure to increased respiratory infection and symptoms, reduced lung growth in children, and increased lung cancer in nonsmoking adults. The more consistent exposure-response data for studies on acute health in children may reflect the greater difficulty in measuring exposure in studies of chronic health in adults.     

Scenarios in Europe—Who uses them and why?

The authors of this article describe a study of European companies the aim of which was to review the extent of multiple scenario analysis in company planning. They describe the differences in planning between users and non-users of the system, and analyse the benefits and drawbacks of using the system.     

Fire Risks in Oil Refineries: Economic Analysis of Camera Monitoring

A probabilistic method is presented to evaluate the economic value of fire monitoring by closed circuit TV camera in petroleum refineries. The proposed model is restricted to the analysis of risk reduction in an area where fires can be caused either by pump failure or by failure of valves and lines. The benefits come from reducing the time during which the fire grows undetected. Fire growth and expected values of losses are analyzed by a Markov model that includes five phases: (1) active undetected growth, (2) detection, (3) fire growth at the beginning of the firemen's intervention, (4) fire control, and (5) fire extinction. The results (e.g., the expected net present value of the investment) show that the proposed monitoring investment is attractive for an illustrative example.     

Evaluating basic research strategies

A model has been developed to describe the pharmaceutical research and drug innovation process. The model originally served to show the range of results that could arise from research in the field of infectious disease chemotherapy over a sustained period of time. The main goal of the model was to illuminate the risk/reward/time tradeoff faced by management in selecting a particular research strategy. The results obtained with this model were one of several considerations influencing the research strategy decision of CIBA-GEIGY in 1976 to adapt and strengthen its research effort in infectious disease chemotherapy.This model has so far been applied only for the comparative evaluation of infectious disease chemotherapy research strategies. However, there is no conceptual reason why it should be limited to this field of drug research or indeed to pharmaceutical research at all. This type of analysis should be applicable wherever clear, product-oriented research goals can be identified and defined, where some reasonable financial reward can be attached to achieving these goals, and where an assessment—albeit subjective—can be made of the likelihood of achieving these goals.     

Mlonte Carlo Techniques for Quantitative Uncertainty Analysis in Public Health Risk Assessments

Most public health risk assessments assume and combine a series of average, conservative, and worst-case values to derive a conservative point estimate of risk. This procedure has major limitations. This paper demonstrates a new methodology for extended uncertainty analyses in public health risk assessments using Monte Carlo techniques. The extended method begins as do some conventional methods--with the preparation of a spreadsheet to estimate exposure and risk. This method, however, continues by modeling key inputs as random variables described by probability density functions (PDFs). Overall, the technique provides a quantitative way to estimate the probability distributions for exposure and health risks within the validity of the model used. As an example, this paper presents a simplified case study for children playing in soils contaminated with benzene and benzo(a)pyrene (BaP).