Biomedical subjects

Zhiyong Xie

Publications and source records attributed to Zhiyong Xie.

12 recordsLinked to original sources

PubMed2006

Rapid and sensitive determination of donepezil in human plasma by liquid chromatography/tandem mass spectrometry: application to a pharmacokinetic study.

A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for the determination of donepezil in human plasma samples. Diphenhydramine was used as the internal standard. The collision-induced transition m/z 380 --> 91 was used to analyze donepezil in selected reaction monitoring mode. The signal intensity of the m/z 380 --> 91 transition was found to relate linearly with donepezil concentrations in plasma from 0.1-20.0 ng/mL. The lower limit of quantification of the LC/MS/MS method was 0.1 ng/mL. The intra- and inter-day precisions were below 10.2% and the accuracy was between -2.3% and +2.8%. The validated LC/MS/MS method was applied to a pharmacokinetic study in which healthy Chinese volunteers each received a single oral dose of 5 mg donepezil hydrochloride. The non-compartmental pharmacokinetic model was used to fit the donepezil plasma concentration-time curve. Maximum plasma concentration was 12.3 +/- 2.73 ng/mL which occurred at 3.50 +/- 1.61 h post-dosing. The apparent elimination half-life and the area under the curve were, respectively, 60.86 +/- 12.05 h and 609.3 +/- 122.2 ng . h/mL. LC/MS/MS is a rapid, sensitive and specific method for determining donepezil in human plasma samples.

Administration, Oral↗

PubMed2005

Atmospheric concentrations and air-sea exchanges of nonylphenol, tertiary octylphenol and nonylphenol monoethoxylate in the North Sea.

Concentrations of nonylphenol isomers (NP), tertiary octylphenol (t-OP) and nonylphenol monoethoxylate isomers (NP1EO) have been simultaneously determined in the sea water and atmosphere of the North Sea. A decreasing concentration profile appeared following the distance increasing from the coast to the central part of the North Sea. Air-sea exchanges of t-OP and NP were estimated using the two-film resistance model based upon relative air-water concentrations and experimentally derived Henry's law constant. The average of air-sea exchange fluxes was -12+/-6 ng m(-2)day(-1) for t-OP and -39+/-19 ng m(-2)day(-1) for NP, which indicates a net deposition is occurring. These results suggest that the air-sea vapour exchange is an important process that intervenes in the mass balance of alkylphenols in the North Sea.

Adsorption↗

PubMed2005

Pharmacokinetic differences between pantoprazole enantiomers in rats.

PURPOSE: The purpose of this study was to quantitatively clarify the contribution of the absorption, protein binding, and metabolism of cytochrome P450 enzymes to the enantioselective pharmacokinetics of pantoprazole enantiomers in rats. METHODS: The enantioselective pharmacokinetics of pantoprazole enantiomers was estimated by an oral administration of racemic pantoprazole to rats. The pharmacokinetic differences between pantoprazole enantiomers were evaluated by the experiments of the in situ perfusion into rat small intestine, the protein binding, and the in vitro metabolism in rat liver microsomes of pantoprazole enantiomers. RESULTS: The mean area under the curve value of S-pantoprazole was 1.5 times greater than that of R-pantoprazole after administration of racemic pantoprazole to rats (20 mg/kg, p.o.). There were significant differences in k(e) (p < 0.05), t1/2 (p < 0.01), and mean residence time (p < 0.01) values between the two enantiomers. In the in situ absorption study, the absorption rate constants were of no significant differences between the two enantiomers. The mean unbound fraction of R-pantoprazole was slightly greater than that of S-pantoprazole. The intrinsic clearance (CLint) of the formation of the 5'-O-demethyl metabolite from S-pantoprazole was 4-fold lower than that from R-pantoprazole. However, the CLint value for the sulfone and 6-hydroxy metabolites from S-pantoprazole was higher than that from R-pantoprazole. The sum of the CLint of the formation of all three metabolites was 3.06 and 4.82 mL/min/mg protein for S- and R-pantoprazole, respectively. CONCLUSIONS: This study suggests that the enantioselective pharmacokinetics of pantoprazole enantiomers in rats is probably ascribable to their enantioselective metabolism, which is contributed by all the three metabolic pathways, including sulfoxide oxidation, 4'-O-demethylation, and 6-hydroxylation.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2005

Apoptosis in primary oral squamous cell carcinomas without lymph node metastases.

The apoptosis in primary oral squamous cell carcinomas (OSCCs) without lymph node (IN) metastases and its relation with clinical stages and pathological grades was investigated. The terminal deoxynucleotidyl trasferase (TdT)-mediated dUTP nick end labeling (TUNEL) was used to detect the apoptotic cells in 15 cases of OSCCs. The percentage of apoptotic cells among tumor cells were calculated as apoptotic index (AI). The results showed that in all 15 cases of OSCCs, apoptotic cells could be visualized by TUNEL with AI ranging from 0.03 to 0.92 (average 0.32). AI was significantly negatively correlated with pathological grades (P < 0.05). It was concluded that the apoptotic rate was related to the malignant degree of OSCCs without LN metastases.

Adult↗

PubMed2005

Characterization of brain plasticity in schizophrenia using template deformation.

RATIONALE AND OBJECTIVE: Abnormal neurodevelopment may play a role in the pathophysiology of schizophrenia. We used deformation-based morphometry to examine voxel-wise age-related changes in patients with schizophrenia compared with healthy brains. MATERIALS AND METHODS: We used a set of skull-stripped brains from an image database of cranial magnetic resonance images. We then deformed a template brain to the rest of the brains creating a set of deformation fields. Using the Jacobian values of these deformation fields, we calculated the voxel-wise t-score for comparison of controls with patients. We also calculated the voxel-wise Pearson correlation of Jacobian with age for both controls and patients. RESULTS: By examining the volume renderings of these statistical fields, we found that healthy people undergo age-related expansion of the ventricles, the surrounding periventricular white matter, and a corresponding decline in the frontal lobes and cingulate gyrus. In contrast, patients show much less of this age-related expansion of the ventricles and less atrophy in the cerebral cortex. In addition, patients have larger ventricles and reduced volume in the frontal/parietal lobes. CONCLUSION: These constellations of findings suggest that otherwise normal age-related ventricular enlargement and cortical loss occurs in schizophrenia patients, albeit at an earlier age.

Adolescent↗

PubMed2005

Regional structural characterization of the brain of schizophrenia patients.

RATIONALE AND OBJECTIVES: We study morphologic characteristics and age-related changes in patients with schizophrenia to investigate whether abnormal neurodevelopment and brain structure have a role in the pathophysiological course of this disease. MATERIALS AND METHODS: Our data consist of a set of cranial magnetic resonance images of 46 patients with schizophrenia and age- and sex-matched healthy controls. We deformed a template brain image to our set of subject images. Jacobian fields of these deformations were reduced to sets of 52 normalized region volumes for each subject by using a neuroanatomic atlas. Normalized regional volumes of the control and patient groups were compared by using Student t-test, and age correlation of each region volume was calculated for the two groups. All results were corrected for multiple comparisons by using permutation testing. We used a classifier based on support vector machines and a feature selection method to determine our ability to discriminate brains of controls from those of patients. RESULTS: Analysis of normalized region volumes shows enlargement of the third ventricle in patients. The age-correlation study showed a significant positive correlation in the third ventricle and right thalamus of controls, but not patients. Using an average of 6.5 features, our classifier was able to correctly identify 72% of patients and 70% of controls. CONCLUSION: In addition to enlargement of the third ventricle, brains of patients with schizophrenia show a different pattern of age-related changes.

Adult↗

PubMed2005

Metabolism of pantoprazole involving conjugation with glutathione in rats.

We have investigated the metabolism of pantoprazole and have provided an explanation for the formation mechanism of its metabolites. Metabolites found in the urine of rats after oral administration of pantoprazole sodium (25 mg kg(-1)) were analysed by liquid chromatography/ion trap mass spectrometry (LC/MS(n)). The N -acetylcysteine derivatives of benzimidazole (M1) and pyridine (M2), four pyridine-related metabolites (M3-M6), and three benzimidazole-related metabolites (M7-M9) were found, none of which had been reported previously. Five of the metabolites (M1, M2, M3, M7, and M8) were isolated from the urine of rats after oral administration of pantoprazole sodium by semipreparative HPLC. Structures of these metabolites were identified by a combination analysis of LC/MS(n) and (1)H NMR spectra. Structures of the remaining four metabolites (M4, M5, M6, and M9) were tentatively assigned through LC/MS(n). The metabolites M2, M3, M4, M5 and M6 and the other metabolites (M1, M7, M8, and M9) reflected the fate of the pyridine moiety and the benzimidazole moiety, respectively. The proposed formation route of M3-M6 was via initial reduction to mercaptopyridine followed by S-methylation, O-demethylation, and S-oxidation to the corresponding sulfoxide or sulfone. Meanwhile, M8 and M9 were formed via initial reduction to the 5-difluoromethoxy-1H benzoimidazole-2-thiol (M7) followed by hydroxylation and S-methylation. The metabolism of pantoprazole included an attack by glutathione on the benzimidazole-2-carbon and pyridine-7'-carbon. It is an important metabolic pathway of pantoprazole in rats.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2003

Detection of the gasoline components methyl tert-butyl ether, benzene, toluene, and m-xylene using ion mobility spectrometers with a radioactive and UV ionization source.

For the first time, ion mobility spectrometers (IMS) with radioactive and UV ionization sources in combination with multicapillary columns (MCCs) have been used to determine methyl tert-butyl ether (MTBE), a gasoline additive, in water and nitrogen as well as the monoaromatic compounds benzene, toluene, and m-xylene (BTX). A membrane extraction unit was set up to extract the substances from water, which is simple, effective, and easy to automate for further applications. Thus, the detection of MTBE and BTX of gasoline vapors was accomplished after a preliminary silicone membrane extraction. Two-dimensional data analyses of IMS-chromatograms allow us to separate these substances clearly according to their different retention and drift times. Method detection limits for MTBE were 2 microg/L (UV) and 30 pg/L (63Ni) in nitrogen and 20 mg/L (UV) and 1 microg/L (63Ni) in water. Rather a good reproducibility was achieved with relative standard deviations of between 2.9 and 9%. The method presented in this article has been proven to be suitable for nearly real-time monitoring as the total analysis time is less than 90 s. As an example of application, the detection of MTBE and BTX in a mixture of volatile organic compounds of pure gasoline using the 2-D IMS-chromatogram is presented.

Journal Article↗

PubMed2003

Determination of carbocysteine in human plasma by liquid chromatography/tandem mass spectrometry employing precolumn derivatization.

A sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed to determine carbocysteine in human plasma using 2-pyridylacetic acid as the internal standard (IS). The method employed derivatization with 10 M hydrochloric acid/methanol, which significantly improved the ionization efficiency of carbocysteine. After methanol-induced protein precipitation of plasma samples, carbocysteine and the IS were derivatized and subjected to LC/MS/MS analysis using atmospheric pressure chemical ionization. The method has a lower limit of quantitation of 20 ng/mL for a 0.2-mL plasma aliquot. The intra- and inter-day precision (RSD), calculated from quality control (QC) samples, was less than 7%. The accuracy, determined using QC samples, was within +/- 1%. The method offered increased sensitivity, selectivity and speed of analysis over existing methods. The method was utilized to support clinical pharmacokinetic studies of carbocysteine in volunteers following oral administration.

Calibration↗

PubMed2003

Alzheimer's disease and frontotemporal dementia exhibit distinct atrophy-behavior correlates: a computer-assisted imaging study.

RATIONALE AND OBJECTIVES: The purpose of this study was to test the hypothesis that distinct patterns of gray matter atrophy are responsible for unique interruptions of the naming process in Alzheimer's disease (AD) and frontotemporal dementia (FTD). MATERIALS AND METHODS: Voxel-based morphometry (VBM) was performed to characterize at the voxel level the neuroanatomic changes that occur in AD and FTD based on high-resolution T1-weighted three-dimensional (3D) spoiled-gradient echo images of patients (AD, n = 12; FTD, n = 29) and healthy control subjects (n = 12). The cortical atrophy measurements were correlated with performance on behavioral measures of naming and related processes to identify brain regions that may contribute to this language function. RESULTS: Both AD and FTD have significant naming difficulty, and this difficulty in naming correlates with a measure of lexical retrieval in both patient groups as well. However, only FTD patients showed a correlation with semantic memory. Areas of cortical atrophy common to AD and FTD were found in the anterior temporal, posterolateral temporal, and dorsolateral prefrontal regions of the left hemisphere. Correlation with naming in both AD and FTD was seen in the left anterior temporal cortex, suggesting that this area may play a role in the lexical retrieval component of naming. We also observed several unique areas of cortical atrophy in temporal and frontal cortices of these patients. Right anterior temporal and left posterolateral temporal regions of atrophy correlated with naming difficulty in FTD, suggesting that these areas may contribute to the semantic memory component of naming. Cortical areas correlating with naming that are not atrophic may represent regions that play an optional role in naming. CONCLUSION: VBM provides an important first step in analyzing brain-behavior relations in vivo in patients with neurodegenerative diseases. More refined analyses of brain morphology via high-dimensional normalization methods that are capable of modeling local as well as global variability in neuroanatomical structure promise to be even more informative.

Aged↗

PubMedDate not supplied

Simultaneous determination of pantoprazole and its two metabolites in dog plasma by HPLC.

A simple and sensitive high-performance liquid chromatography (HPLC) method is developed and validated for simultaneous determination of pantoprazole and its two metabolites (pantoprazole sulfone and pantoprazole thioether) in dog plasma and applied to a pharmacokinetic study in Beagle dogs. Following a protein precipitation procedure, the samples are separated using reversed-phase HPLC (C18) by a gradient of acetonitrile and ammonium acetate (pH 6.0) at a flow rate of 1.0 mL/min and quantitated using UV detection at 290 nm. Omeprazole is selected as the internal standard. The method has a lower limit of quantitation of 0.025 microg/mL for pantoprazole and its two metabolites, using 0.1-mL aliquots of plasma. The linear calibration curves are obtained in the concentration range of 0.025-10.0 microg/mL for three analytes. The intra- and interrun precision (relative standard deviation), calculated from quality control (QC) samples, is less than 13% for three analytes. The accuracy determined from QC samples is between -6.4% and 12%.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMedDate not supplied

Image registration using hierarchical B-splines.

Hierarchical B-splines have been widely used for shape modeling since their discovery by Forsey and Bartels. In this paper, we present an application of this concept, in the form of free-form deformation, to image registration by matching two images at increasing levels of detail. Results using MRI brain data are presented that demonstrate high degrees of matching while unnecessary distortions are avoided. We compare our results with the nonlinear ICP (Iterative Closest Point) algorithm (used for landmark-based registration) and optical flow (used for intensity-based registration).

Algorithms↗