Alzheimer Disease: Chen SH

Kareken DA, Doty RL, Moberg PJ, Mosnik D, Chen SH, Farlow MR, Hutchins GD. · Department of Neurology, Indiana University School of Medicine, Indianapolis 46202, USA. · Neuropsychology. · Pubmed #11216885 No free full text.

Abstract: Olfaction is impaired in Alzheimer's disease (AD). It was hypothesized that AD would reduce olfactory-evoked perfusion in mesial temporal olfactory (piriform) cortex, where neuropathology begins. Seven AD patients and 8 elderly controls (ECs) underwent olfactory threshold and identification tests and olfactory stimulation during positron emission tomography. Odor identification was impaired in AD, but threshold was not. Olfactory stimulation in ECs activated right and left piriform areas and right anterior ventral temporal cortex. AD patients had less activation in right piriform and anterior ventral temporal cortex but not in the left piriform area. Although orbital cortex did not activate in ECs, there was a significant between-groups difference in this area. Right piriform activation correlated with odor identification. Impaired odor identification likely reflects sensory cortex dysfunction rather than cognitive impairment. Given olfactory bulb projections to the mesial temporal lobe, olfactory stimulation during functional imaging might detect early dysfunction in this region.

Hsieh YH, Yang YH, Yeh HH, Lin PC, Chen SH. · Faculty of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. · Electrophoresis. · Pubmed #19170055 No free full text.

Abstract: A simple and sensitive MEKC with UV detection was developed and validated for the simultaneous determination of acetylcholinesterase inhibitors including galantamine, rivastigmine and major metabolite NAP 226-90 in plasma. A sample pretreatment by liquid-liquid extraction with diethylether and subsequent quantification by MEKC was used. The optimum separation for these analytes was achieved in <10 min at 25 degrees C with a fused-silica capillary column of 30.2 cm x 50 microm id (effective length 20 cm) and a run buffer containing 25 mM Tris buffer (pH 5.0) with 160 mM sodium octanesulfonate, 20% ACN and 0.01% PVP as a dynamic coating to reduce analytes' interaction with the capillary wall. For sensitivity consideration regarding the determination of linearity, LOD, quantitation and monitoring drugs concentration in patients, the detection wavelengths for galantamine or rivastigmine and NAP 226-90 were set at 214 or 200 nm, respectively. One male volunteer (26-year-old) was orally administered a single dose of 4.5 mg rivastigmine (Exelon, Novartis) in capsule, and blood samples were drawn over a 12 h period for concentration-time profile study. The method was also successfully applied for monitoring galantamine or rivastigmine and its metabolite NAP 226-90 in 11 Alzheimer's disease patients' plasma after oral administration of the commercial products Reminyl (8 mg galantamine/capsule) or Exelon (3 mg rivastigmine/capsule), respectively.

Yeh HH, Yang YH, Ko JY, Chen SH. · Faculty of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Taiwan. · Electrophoresis. · Pubmed #18803179 No free full text.

Abstract: Field-amplified sample stacking (FASS) in capillary electrophoresis (CE) was used to determine the concentration of donepezil, an acetylcholinesterase inhibitor, in human plasma. A sample pretreatment by liquid-liquid extraction with isopropanol/n-hexane (v/v 3:97) and subsequent quantification by FASS-CE was used. Before sample loading, a water plug (0.5 psi, 6 s) was injected to permit FASS. Electrokinetic injection (7 kV, 90 s) was used to introduce sample cations. The separation condition for donepezil was performed in electrolyte solutions containing Tris buffer (60 mM, pH 4.0) with sodium octanesulfonate 40 mM and 0.01% polyvinyl alcohol as a dynamic coating to reduce analytes' interaction with capillary wall. The separation was performed at 28 kV and detected at 200 nm. Using atenolol as an internal standard, the linear ranges of the method for the determination of donepezil in human plasma were over a range of 1-50 ng/mL. The limit of detection was 0.1 ng/mL (S/N=3, sampling 90 s at 7 kV). One female volunteer (54 years old) was orally administered a single dose of 10 mg donepezil (Aricept, Eisai), and blood samples were drawn over a 60 h period for pharmacokinetic study. The method was also applied successfully to monitor donepezil in sixteen Alzheimer's disease patients' plasmas.