Exploring isoxazoles and pyrrolidinones decorated with the 4,6‐dimethoxy‐1,3,5‐triazine unit as human farnesyltransferase inhibitors

Unprecedented triazinyl‐isoxazoles were afforded via an effective cycloaddition reaction between nitrile oxides and the scarcely described 2‐ethynyl‐4,6‐dimethoxy‐1,3,5‐triazine as dipolarophile. The biological evaluation of the newly synthesized compounds showed that the inhibition of human farnesyltransferase by zinc complexation could be improved with triazine‐isoxazole moieties. The replacement of the isoxazole unit by a pyrrolidin‐2‐one was detrimental to the inhibitory activity while the pyrrolidin‐2‐thione derivatives conserved the biological potential. The potential of selected compounds to disrupt protein farnesylation in Chinese hamster ovary (CHO) cells transfected with pEGFP‐CAAX was also evaluated.     

Context and dating of Aurignacian vulvar representations from Abri Castanet, France

We report here on the 2007 discovery, in perfect archaeological context, of part of the engraved and ocre-stained undersurface of the collapsed rockshelter ceiling from Abri Castanet, Dordogne, France. The decorated surface of the 1.5-t roof-collapse block was in direct contact with the exposed archaeological surface onto which it fell. Because there was no sedimentation between the engraved surface and the archaeological layer upon which it collapsed, it is clear that the Early Aurignacian occupants of the shelter were the authors of the ceiling imagery. This discovery contributes an important dimension to our understanding of the earliest graphic representation in southwestern France, almost all of which was discovered before modern methods of archaeological excavation and analysis. Comparison of the dates for the Castanet ceiling and those directly obtained from the Chauvet paintings reveal that the "vulvar" representations from southwestern France are as old or older than the very different wall images from Chauvet.     

Indications for and results of arthroscopy in the arthritic knee: a European survey

Purpose

The place of arthroscopic treatment in osteoarthritis of the knee has generated much controversy. A survey was initiated to collect the opinion of experienced surgeons.

Methods

Of the 211 surgeons interviewed, 170 (80.6 %) replied to the electronic questionnaire. Respondents had at least ten years of experience in arthroscopy and currently perform more than 100 arthroscopies per year. Various indications and treatment modalities for arthroscopy in osteoarthritis of the knee had to be evaluated on a scale from “excellent” to “no indication”.

Results

The respondents generally believe that an improvement is more likely in low-grade osteoarthritis (p < 0.001) and in neutral leg axis (p < 0.001). The outcome was rated better if symptoms had persisted for less than six months (p < 0.001) and for patients that were younger than 60 years (p < 0.001). Partial meniscectomy and notchplasty in cases of extension deficit were considered as successful treatment options. Debridement was an accepted indication, with an outcome mainly rated as fair. A majority saw no indication for joint lavage, arthroscopic treatment of arthrofibrosis and removal of osteophytes. The outcome appears to be poor if a bone edema is diagnosed on magnetic resonance imaging prior to arthroscopy. Only 55.9 % of respondents were comfortable with the current definition of osteoarthritis.

Conclusions

Experienced arthroscopic surgeons all over Europe believe arthroscopy in osteoarthritis is appropriate, under certain conditions. The major task for surgeons is to select the right patients who are likely to benefit from this intervention.