Increasing evidence demonstrates that there is marked damage and dysfunction in the white matter in Alzheimer's disease (AD). The present study investigates the nature of white matter damage of patients with Alzheimer's disease with diffusion tensor magnetic resonance imaging (DTI) and analyses the relationship between the white matter damage and the cognition function. DTI, as well as T1 fluid attenuated inversion recovery (FLAIR) and T2-FLAIR, was performed on probable patients of Alzheimer's disease, and sex and age matched healthy volunteers to measure the fractional anisotropy (FA) and mean diffusivity (MD) in the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, and the white matter of frontal, temporal, parietal, and occipital lobes.
View Article and Find Full Text PDFAmyotrophic lateral sclerosis (ALS), the most common motor neuron disease, is caused by a selective loss of motor neurons in the CNS. Mutations in the ALS2 gene have been linked to one form of autosomal recessive juvenile onset ALS (ALS2). To investigate the pathogenic mechanisms of ALS2, we generated ALS2 knock-out (ALS2(-/-)) mice.
View Article and Find Full Text PDFEnzymatic transesterification of glucose with the vinyl ester of non-steroidal anti-inflammatory drugs (NSAIDs) was in organic media performed for synthesis of novel NSAIDs-glucose conjugates. Glucose was regioselectively acylated at the 6-hydroxyl group. The indomethacin-glucose conjugate and ketoprofen-glucose conjugate were produced by the catalysis of alkaline protease from Bacillus subtilis in the respective yields of 42% (over 48 h) and 63% (over 40 h).
View Article and Find Full Text PDFBioorg Med Chem Lett
September 2005
Selectivity of enzymatic and chemical methods for transesterifications of cytarabine with divinyl dicarboxylates was described. Catalysis by lipase acrylic resin from Candida antarctica (CAL-B) in acetone facilitated the single step synthesis of polymerizable 5'-O-acyl cytarabine derivatives in high yields, while the use of alkaline protease from Bacillus subtilis (subtilisin) in pyridine afforded the mixture products of 5'-O-acyl and 4-N-acyl cytarabine derivatives. Interestingly, polymerizable 4-N-acyl cytarabine vinyl derivatives can be selectively prepared by chemical transesterification in dioxane.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by overproduction of beta-amyloid (Abeta), with the subsequent pathologic deposition of Abeta which is important for memory and cognition. Recent studies showed murine models of AD and AD patients inoculated with Abeta(1-42) peptide vaccine had a halted or delayed pathological progression of AD. Unfortunately, the clinical phase IIa trial of Abeta(1-42) peptide vaccine (AN1792) was halted prematurely because of episodes of menigoencephalitis in 18 of the vaccinated patients.
View Article and Find Full Text PDFThree beta-cyclodextrin (beta-CD) conjugates of non-steroidal anti-inflammatory drugs were synthesized by enzymatic methods. Transesterification of beta-CD with vinyl ester of indomethacin, ketoprofen and etodolac was performed by the catalysis of alkaline protease from Bacillus subtilis in anhydrous DMF for 3 days. The drug molecules were selectively conjugated onto one of the secondary hydroxyl groups of beta-CD through ester-linkage to improve their poor water solubility and absorption characteristics.
View Article and Find Full Text PDFXi Bao Yu Fen Zi Mian Yi Xue Za Zhi
March 2005
Aim: To observe the humoral immuneresponse in Rhesus monkey induced by Abeta42 peptide vaccination.
Methods: Five male Rhesus monkeys were received intramuscular injection of Abeta42 peptide vaccine at 0, 2nd, 6th, 10th, 14th, 18th, 22th week. The titers and Ig subclasses of the serum anti-Abeta42 antibody were measured by ELISA.