Enantioselective Synthesis and Conformational Analysis of Cyclohexene Carbocyclic Nucleosides

Abstract

An enantioselective approach towards the synthesis of optically pure cyclohexene nucleosides 3 has been developed starting from (R)-carvone. The key steps are the regio- and stereoselective hydroboration of an exo double bond, the selective reduction of an enone intermediate and introduction of a base moiety by Mitsunobu reaction. Conformational analysis showed that the adenine base adopts predominantly in a pseudo-axial position.     

Anti-Hiv-1 Activity of 2′,3′-Dideoxinucleoside Analogues : Structure-Activity Relationship

Abstract

Among the purine and pyrimidine 2′,3′-dideoxynucleosides, 2′,3′-didehydro-2′,3′-dideoxynucleosides, 3′-azido-2′,3′-dideoxynucleosides and 3′-fluoro-2′,3′-dideoxynucleosides, several congeners have been identified which achieve a potent and selective inhibition of HIV-1 replication in vitro.     

Synthesis of 1,5-Anhydrohexitol Nucleosides as Mimics of AZT,D4T and DDC

Abstract

1,5-Anhydrohexitol congeners of AZT, D4T and DDC were synthesized. These compounds did not show anti-HIV activity.

     

Ribosylation of Pyrimidine 2′-Deoxynucleosides

Abstract

The previously developed method for the preparation of 2′-O-D-ribofuranosyl-nucleosides is extended to ribosylation of 2′-deoxynucleosides. The scope and limitations of this reaction are discussed.     

Altered Dihydropyrimidine Dehydrogenase Activity Associated with Mild Toxicity in Patients Treated with 5-Fluorouracil Containing Chemotherapy

Dihydropyrimidine dehydrogenase (DPD) plays a pivotal role in the metabolism of 5-fluorouracil (5FU). In patients treated with capecitabine or 5FU combined with other chemotherapeutic drugs, DPD activity in peripheral blood mononuclear cells was increased in patients experiencing grade I/II neutropenia. In contrast, decreased DPD activity proved to be associated with grade I/II dermatological toxicity, including hand-foot syndrome. Thus, patients with a low-normal or high-normal DPD activity proved to be at risk of developing mild toxicity upon treatment with 5FU-based chemotherapy, demonstrating the important role of DPD in the etiology of toxicity associated with 5FU and the catabolites of 5FU.     

The relative influence of catchment, riparian corridor, and reach-scale anthropogenic pressures on fish and macroinvertebrate assemblages in French rivers

This study compares the relative influences of physiography and anthropogenic pressures on river biota at catchment, riparian corridor, and reach scales. Environmental data, catchment and riparian corridor land use, anthropogenic modifications and biological data were compiled for 301 French sites sampled from 2005 to 2008. First, relationships between anthropogenic pressures and fish and macroinvertebrate assemblages were analysed using redundancy analysis. Second, the influences of physiography and the three scales of human pressures on biological assemblages were measured using variance partitioning. Distributions of fish and macroinvertebrate taxa along the pressure gradients agreed with bio-ecological knowledge. At the reach scale, assemblage variability among the 301 French sites was related to the presence of an impoundment and to poor water quality, while at larger scales it was linked to a gradient from forest to agricultural covers. In addition, a large proportion of the explained variability in assemblage composition was related to complex interactions among factors (~40%) and to physiographic variables (~30%). Furthermore, our results highlight that catchment land use better reflects local water quality impairments than hydromorphological degradations. Finally, this study supports the idea that human pressure effects on river communities are linked at several spatial scales and must be considered jointly.     

At the edge and on the top: molecular identification and ecology of Daphnia dentifera and D. longispina in high-altitude Asian lakes

The occurrence of members of the highly diverse Daphnia longispina complex in Southern and Central Asian high-mountain lakes has been recognized for more than a century. Until now, however, no molecular data have been available for these populations inhabiting the “Roof of the World.” Here, we present the first identification for D. gr. longispina from that region based on a molecular phylogeny. Our findings show that alpine lakes in the Pamir and Himalaya mountains host populations of widespread species of the complex, for which these are the highest known localities. A spineless morph from the Himalaya region, previously labeled as D. longispina var. aspina, was clustering tightly with D. dentifera, while a population from the Pamir mountain range was grouped with D. longispina. In addition, we analyzed ecological data available for lakes in the Khumbu region (Himalaya) to investigate ecological preferences of non-pigmented D. gr. longispina. The identified factors can at least partly be related to avoidance of high UV conditions by this species. We conclude that the widespread species D. dentifera and D. longispina also colonized the Asian high-mountain lakes, and identify the need for further research to trace the possible effect of rapid environmental changes in this region on the diversity and ecology of high-altitude Daphnia populations.     

Protocol of a prospective study on the diagnostic value of transcranial duplex scanning of the substantia nigra in patients with parkinsonian symptoms

Background  

Parkinson's disease (PD) is the second most common neurodegenerative disorder. As there is no definitive diagnostic test, its diagnosis is based on clinical criteria. Recently transcranial duplex scanning (TCD) of the substantia nigra in the brainstem has been proposed as an instrument to diagnose PD. We and others have found that TCD scanning of substantia nigra duplex is a relatively accurate diagnostic instrument in patients with parkinsonian symptoms. However, all studies on TCD so far have involved well-defined, later-stage PD patients, which will obviously lead to an overestimate of the diagnostic accuracy of TCD.