A probiotic fermented dairy drink improves antibody response to influenza vaccination in the elderly in two randomised controlled trials.

Background: Influenza vaccination is recommended for the elderly in many countries, but immune responses are weaker compared to younger adults.

Objective: To investigate the impact of daily consumption of a probiotic dairy drink on the immune response to influenza vaccination in an elderly population of healthy volunteers over 70 years of age.

Design: Two randomised, multicentre, double-blind, controlled studies were conducted during two vaccination seasons in 2005-2006 (pilot) and 2006-2007 (confirmatory).

A systematic SAR study of C10 modified paclitaxel analogues using a combinatorial approach.

A library with 63 paclitaxel analogues modified at the C10 position of paclitaxel has been prepared using parallel solution phase synthesis. Most of the C10 analogues were slightly less active than paclitaxel in the tubulin assembly assay and had reduced potency in the B16 melanoma and MCF-7 cell line cytotoxicity assays. These modifications at C10, however, did not lead to the total loss of activity, indicating that the C10 moiety of paclitaxel may not be directly involved in the drug-microtubule interactions, but could influence its binding affinity to P-glycoprotein.

Total synthesis of cryptophycin-24 (Arenastatin A) amenable to structural modifications in the C16 side chain.

Two efficient protocols for the synthesis of tert-butyl (5S,6R,2E, 7E)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-8-phenyl-2, 7-octadienoate, a major component of the cryptophycins, are reported. The first utilized the Noyori reduction and Frater alkylation of methyl 5-benzyloxy-3-oxopentanoate to set two stereogenic centers, which became the C16 hydroxyl and C1' methyl of the cryptophycins. The second approach started from 3-p-methoxybenzyloxypropanal and a crotyl borane reagent derived from (-)-alpha-pinene to set both stereocenters in a single step and provided the dephenyl analogue, tert-butyl (5S,6R,2E)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-2, 7-octadienoate, in five steps.

Conformationally restricted paclitaxel analogues: macrocyclic mimics of the "hydrophobic collapse" conformation.

Conformationally restricted macrocyclic analogues of paclitaxel were prepared, by connecting the 3'-phenyl group and the 2-benzoate moiety with two-atom tethers to mimic the "hydrophobic collapse" paclitaxel conformation. The analogues did not show activity in a tubulin assembly assay.

The oxetane conformational lock of paclitaxel: structural analysis of D-secopaclitaxel.

Analysis of the 1H NMR data of paclitaxel in comparison with its oxetane ring-opened analogue D-secopaclitaxel suggests that the oxetane moiety (D-ring) of paclitaxel serves as a conformational lock for the diterpene moiety and the C13 side chain.