Aspirin-like drugs may block pain independently of prostaglandin synthesis inhibition

Summary Using flurbiprofen, a chiral anti-inflammatory and analgesic 2-arylpropionic acid derivative, the enantiomers of which are not converted to each other (less than 5%) in rats or man, we obtained evidence that prostaglandin synthesis inhibition is primarily mediating the anti-inflammatory activity but prostaglandin synthesis independent mechanisms contribute to the analgesic effects. Thus, the S-form inhibited prostaglandin synthesis, inflammation and nociception in rats. The R-form had much less effect on prostaglandin synthesis and did not affect inflammation. It did, however, block nociception in rats almost as potently as the S-form. S-flurbiprofen, in contrast to the R-form, was clearly ulcerogenic in the gastrointestinal mucosa. These results indicate additional molecular mechanisms of analgesia and suggest the use of R-arylpropionic acids as analgesics.     

Subset threshold autoregression

We develop in this paper an efficient way to select the best subset threshold autoregressive model. The proposed method uses a stochastic search idea. Differing from most conventional approaches, our method does not require us to fix the delay or the threshold parameters in advance. By adopting the Markov chain Monte Carlo techniques, we can identify the best subset model from a very large of number of possible models, and at the same time estimate the unknown parameters. A simulation experiment shows that the method is very effective. In its application to the US unemployment rate, the stochastic search method successfully selects lag one as the time delay and five best models from more than 4000 choices. Copyright © 2003 John Wiley & Sons, Ltd.     

Genotoxic effects of dithane M-45 on the bone marrow cells of mice in vivo

Genotoxic effects of dithane M-45 were studied on the bone marrow cells of male albino mice (Lacca strain) in vivo. Different doses (30 mg, 40 mg and 300 mg/kg b.wt) of dithane M-45 were injected intraperitoneally and their effects were investigated after time intervals of 1, 2, 5 and 10 days. The chromosomal aberrations observed in the bone marrow cells of male mice after treatment with dithane M-45 were fragments, rings, dicentric chromosomes, terminal chromatid deletions, chromatid gaps and breaks. In addition to these chromosomal aberrations, physiological effects such as uneven stretching of chromatin material, end-to-end chromosomal associations, exchange configurations, clumping, stickiness and centromeric associations were also observed.     

Sister chromatid exchanges in lymphocytes of normal and alcoholic subjects.

The effects of alcohol consumption, cigarette smoking and age on sister chromatid exchange (SCE) frequency in human lymphocytes were assessed by means of multiple linear regression. An increase in SCE rates was associated with alcohol consumption (p = 0.0001), smoking (p = 0.0231), and, to a small extent (p = 0.057), age. These three confounding factors explain 48% of the inter-personal variation in SCE rates among subjects studied.