Trace analysis of acetylcholinesterase inhibitors with antipsychotic drugs for Alzheimer's disease by capillary electrophoresis with on column field-amplified sample injection.

A simple and sensitive capillary zone electrophoresis (CZE) with UV detection (214 nm) was developed and validated for the simultaneous determination of the acetylcholinesterase inhibitors (AChEI), donepezil, and rivastigmine, with antipsychotic drugs in plasma. A sample pretreatment by liquid-liquid extraction and subsequent quantification by CZE with field-amplified sample injection (FASI) was used. The optimum separation for these analytes was achieved in <20 min at 25 °C with a fused-silica capillary column of 60.2 cm × 50 µm I.D. (effective length 50 cm) and a run buffer containing 120 mM phosphate (pH 4.0) with 0.1 % γ-cyclodextrin, 40 % methanol (MeOH), and 0.02 % polyvinyl alcohol as a dynamic coating to reduce analytes' interaction with the capillary wall. Using phenformin as an internal standard (40.0 ng/mL), the linear ranges of the proposed method for the simultaneous determination of donepezil, rivastigmine, aripiprazole, quetiapine, risperidone, clozapine, ziprasidone, and trazodone were over the range 4.0-80.0 ng/mL, and olanzapine was over the range 1.0-20.0 ng/mL. The method was applied for concentrations monitoring of AChEIs and antipsychotic drugs in ten Alzheimer's disease patients with behavioral and psychological symptoms of dementia after oral administration of the commercial products.

Analysis of quinapril by two solvent-saving methods: application of capillary column high-performance liquid chromatography with ultraviolet absorbance detection and LDI-TOF-MS.

A capillary column high-performance liquid chromatography (CapLC) method and a laser desorption ionization-time of flight (LDI-TOF)-MS method are described for the determination of quinapril, an angiotensin-converting enzyme inhibitor. Effective separation was achieved by using a C18 capillary column at a flow rate of 10 microL/min. For CapLC, quinapril and 7-hydroxycoumarin (internal standard) were detected at 210 and 320 nm, respectively. Phenformin replaced 7-hydroxycoumarin as the internal standard for the LDI-TOF-MS method successfully developed to detect quinapril. The calibration curves showed good linearity in the range of 1-100 micro/mL in these two methods. For high throughput purposes, the LDI-TOF-MS method was simpler and faster than the CapLC method. Both green methods were suitably validated and successfully applied to determine quinapril in commercial tablets.

Kabuki syndrome: review of the clinical features, diagnosis and epigenetic mechanisms.

BACKGROUND: Kabuki syndrome (KS), is a infrequent inherited malformation syndrome caused by mutations in a H3 lysine 4 methylase (KMT2D) or an X-linked histone H3 lysine 27 demethylase (UTX/KDM6A). The characteristics in patients with KS have not yet been well recognized. DATA SOURCES: We used databases including PubMed and Google Scholar to search for publications about the clinical features and the etiology of Kabuki syndrome. The most relevant articles to the scope of this review were chosen for analysis. RESULTS: Clinical diagnosis of KS is challenging in initial period, because many clinical characteristics become apparent only in subsequent years. Recently, the genetic and functional interaction between KS-associated genes and their products have been elucidated. New clinical findings were reported including nervous system and intellectual performance, endocrine-related disorders and immune deficiency and autoimmune disease. Cancer risks of Kabuki syndrome was reviewed. Meanwhile, we discussed the Kabuki-like syndrome. Digital clinical genetic service, such as dysmorphology database can improve availability and provide high-quality diagnostic services. Given the significant clinical relevance of KS-associated genes and epigenetic modifications crosstalk, efforts in the research for new mechanisms are thus of maximum interest. CONCLUSIONS: Kabuki syndrome has a strong clinical and biological heterogeneity. The main pathogenesis of Kabuki syndrome is the imbalance between switch-on and -off of the chromatin. The direction of drug research may be to regulate the normal opening of chromatin. Small molecule inhibitors of histone deacetylases maybe helpful in treatment of mental retardation and reduce cancer risk in KS.

Utilization of magnetic nanobeads for analyzing haptoglobin in human plasma as a marker of Alzheimer's disease by capillary electrophoretic immunoassay with laser-induced fluorescence detection.

Alzheimer's disease (AD) is a neurodegenerative disorder resulting from an impaired cholinergic function with loss of cognitive activity in the brain. Haptoglobin is a useful biomarker for AD analysis. Compared to the conventional enzyme-linked immunosorbent assay for haptoglobin analysis, the proposed immunoassay procedure reduces sample analysis time by approximately 55 min. Therefore, immunoassay was coupled with capillary electrophoresis (CE) to determine haptoglobin concentrations indirectly by using magnetic nanobeads (MBs) as a support and laser-induced fluorescence detection. In human plasma sample, the haptoglobin was immobilized on the MBs and reacted with the purified anti-haptoglobin antibody. The optimum separation time for the analyte was shorter than 6 min at 25 °C with a fused-silica capillary column of 40.2 cm × 50 µm ID (effective length 30 cm) and a run buffer containing 25 mM phosphate (pH 8.0) with 0.01% poly(ethylene oxide) (PEO). When using Atto 495 NHS ester as an internal standard (IS) (250.0 ng mL(-1)), the linear range of the proposed method for indirect determination of haptoglobin was 0.2-3.0 mg mL(-1). The method was further used to monitor the course of AD in patients with behavioral and psychological symptoms of dementia (BPSD).

Serotype distribution and resistance genes associated with macrolide and fluoroquinolone resistance in Streptococcus agalactiae isolates from a hospital in southern Taiwan.

BACKGROUND: Antimicrobial resistance of Streptococcus agalactiae (Group B Streptococcus, GBS) has been emerging worldwide. We aimed to examine the correlation of drug-resistant genes with serotypes and with the mutations of the quinolone resistance-determining region (QRDR) in GBS isolates. METHODS: A total of 323 human GBS isolates were collected from a hospital in southern Taiwan. Laboratory investigation included serotyping by a multiplex polymerase chain reaction (PCR) method, antimicrobial susceptibility testing by a disc diffusion method, and mechanism analysis of the resistance to macrolides and fluoroquinolones by PCR and sequencing methods. RESULTS: Multiplex PCR showed that the most prevalent serotypes were Ib, III, V, and VI, mostly isolated from urine. The ermB gene was highly prevalent in serotypes Ib and V and was associated with clindamycin and macrolide resistance. GBS with a serine-to-leucine mutation at codon 81 in GyrA and with a serine-to-phenylalanine or -tyrosine mutation at codon 79 in ParC had a higher minimum inhibitory concentration of levofloxacin than isolates with only an aspartic acid-to-tyrosine mutation at codon 83 (>32 µg/ml vs. 16 µg/ml) in GyrA. CONCLUSIONS: The most prevalent GBS serotypes were Ib, III, V, and VI. The ermB and mefE genes carried in serotypes Ib and V were highly associated with the resistance to macrolides and clindamycin. Mutations at codon 79 and codon 83 of ParC were the major determining factors for high-level fluoroquinolone resistance.