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Biomedical subjects

Yu-Mei Tan

Publications and source records attributed to Yu-Mei Tan.

9 recordsLinked to original sources

A novel amperometric immunosensor based on Fe3O4 magnetic nanoparticles/chitosan composite film for determination of ferritin.

A novel amperometric immunosensor was developed by immobilizing ferritin antibody (FeAb) on the surface of Fe(3)O(4) magnetic nanoparticles/chitosan composite film modified glassy carbon electrode (GCE). This material combined the advantages of inorganic Fe(3)O(4) nanoparticles with the organic polymer chitosan. The stepwise assembly procedure of the immunosensor was characterized by means of differential pulse voltammetry (DPV) and ac impedance. The K(3)Fe(CN)(6)/K(4)Fe(CN)(6) was used as a marker to probe the interface and to determinate ferritin. The factors that could influence the performance of the resulting immunosensor were studied in detail. After the immunosensor was incubated with ferritin for 32 min at 35 degrees C, the DPV current decreased linearly with the logarithm of ferritin concentration in the range from 20 to 500 ng mL(-1) with a correlation coefficient of 0.995 and a detection limit of 7.0 ng mL(-1). This immunosensor was used to analyze ferritin in human serum samples. The analytical results showed that the developed immunoassay was comparable with the radioimmunoassay (RIA), and the studied immunosensor exhibited good accuracy, high sensitivity, and long-term stability for 3 weeks, which implies a promising alternative approach for detecting ferritin in clinical diagnosis.

Chitosan↗

Reverse dosimetry: interpreting trihalomethanes biomonitoring data using physiologically based pharmacokinetic modeling.

Biomonitoring data provide evidence of exposure of environmental chemicals but are not, by themselves, direct measures of exposure. To use biomonitoring data in understanding exposure, physiologically based pharmacokinetic (PBPK) modeling can be used in a reverse dosimetry approach to assess a distribution of exposures possibly associated with specific blood or urine levels of compounds. Reverse dosimetry integrates PBPK modeling with exposure pattern characterization, Monte Carlo analysis, and statistical tools to estimate a distribution of exposures that are consistent with biomonitoring data in a population. The present study used an existing PBPK model for chloroform as a generic framework to develop PBPK models for other trihalomethanes (THMs). Using Monte Carlo sampling techniques, probabilistic information about pharmacokinetics and exposure patterns was included to estimate distributions of THMs concentrations in blood in relation to various exposure patterns in a diverse population. In addition, the possibility of inhibition of hepatic metabolism among THMs was evaluated under the scenarios of household exposure. These studies demonstrated how PBPK modeling can be used as a tool to estimate a population distribution of exposures that could have resulted in particular biomonitoring results. When toxicity level is known, this tool can also be used to estimate proportion of population above levels associated with health risk.

Animals↗

Pharmacokinetic modeling of saturable, renal resorption of perfluoroalkylacids in monkeys--probing the determinants of long plasma half-lives.

Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) compounds associated with surface protection product manufactures are distributed globally. The 3-5-year half-lives, reproductive and liver toxicity in animals, and lack of understanding of the factors regulating retention in the body have led to a world-wide public concern for use of these materials. Using a novel physiologically-motivated pharmacokinetic model for renal clearance, perfluoroalkylacid pharmacokinetics in monkeys was successfully described by renal resorption via high efficiency transporters for both intravenous and oral dosing. Intravenous dosing with both PFOA and PFOS in Cynomolgus monkeys produced time course curves consistent with a two-compartment distribution. Extending the PK model for intravenous dosing to examine blood and urine time course data for repeated oral dosing clearly identified the saturable renal resorption. Resorption depends on kinetic factors for transport (T(mC), transport maximum; K(T), transport affinity) and free fraction in plasma (f(plasma)). For PFOA, these parameters were estimated to be 5mg/(h kg) (T(mC)), 0.055 mg/L (K(T)), and 0.02 (f(plasma)). PFOS has longer half-life and had respective values of 13.6 mg/(h kg), 0.023 mg/L, and 0.025. PFOS appeared to have a higher transport capacity and lower affinity than PFOA. Human kinetics indicates even higher resorption efficiency.

Administration, Oral↗

Use of a physiologically based pharmacokinetic model to identify exposures consistent with human biomonitoring data for chloroform.

Biomonitoring data provide evidence of human exposure to environmental chemicals by quantifying the chemical or its metabolite in a biological matrix. To better understand the correlation between biomonitoring data and environmental exposure, physiologically based pharmacokinetic (PBPK) modeling can be of use. The objective of this study was to use a combined PBPK model with an exposure model for showering to estimate the intake concentrations of chloroform based on measured blood and exhaled breath concentrations of chloroform. First, the predictive ability of the combined model was evaluated with three published studies describing exhaled breath and blood concentrations in people exposed to chloroform under controlled showering events. Following that, a plausible exposure regimen was defined combining inhalation, ingestion, and dermal exposures associated with residential use of water containing typical concentrations of chloroform to simulate blood and exhaled breath concentrations of chloroform. Simulation results showed that inhalation and dermal exposure could contribute substantially to total chloroform exposure. Next, sensitivity analysis and Monte Carlo analysis were performed to investigate the sources of variability in model output. The variability in exposure conditions (e.g., shower duration) was shown to contribute more than the variability in pharmacokinetics (e.g., body weight) to the predicted variability in blood and exhaled breath concentrations of chloroform. Lastly, the model was used in a reverse dosimetry approach to estimate distributions of exposure consistent with concentrations of chloroform measured in human blood and exhaled breath.

Chloroform↗

[Minute chromosome rearrangement detected by human telomeric band painting probes].

In order to assess the value of applying human chromosomal telomeric band painting probes (TBPs) in genetic diagnosis, we used three human telomeric band painting probes in fluorescence in situ hybridization (FISH) to analyze two cases who had a history of habitual abortion and were suspected to carrying a minute translocation. The probes were prepared by microdissection, and the covered regions were 11q23.3-->qter12q24.1-->qter and 22q13.1-->qter, respectively. According to the FISH results, both the cases were cryptic minute translocation carriers. The involved chromosomes were chromosome 11 and 12 in case 1, and chromosome 11 and 22 in case 2. Combined with chromosome G banding, their breakpoints were 11q23.3, 12q24.1, and 22q13.1, respectively. The results showed that the telomeric band painting probes can be used as a tool to determine minute chromosomal abnormality and the precise breakpoints.

Abortion, Habitual↗

[Cytogenetic study of 1780 cases of spontaneous abortion].

OBJECTIVE: To explore the relationship between chromosome anomaly and spontaneous abortion, and to provide useful information for genetic counseling and prenatal diagnosis in reproductive clinic. METHODS: A total of 1 780 patients who had a history of spontaneous abortion before 24 weeks of gestation were enrolled. The lymphocyte culture and harvest were performed according to standard methods. Karyotypes were analyzed by G-banding in all cases and C- banding in some cases in addition. RESULTS: Altogether 57 abnormal karyotypes were found and the overall incidence of chromosomal abnormalities was 3.20% (women 3.32%; men 2.12%). Among them 23 cases were the balanced translocation; 14 cases were the Robertsonian translocation, 3 cases were the complex chromosomal rearrangement, and the other 17 cases were the other abnormalities. In women with 1, 2, 3 or more spontaneous abortion, the incidence of chromosomal abnormalities was 1.7%, 2.3%, and 5.8%, respectively. CONCLUSION: Translocations are the major abnormal karyotpes associated with spontaneous abortions. The chance of finding chromosomal aberration increases with the number of abortions. Chromosomal abnormalities are more common in women with 3 or more spontaneous abortions.

Abortion, Spontaneous↗

Biologically motivated computational modeling of chloroform cytolethality and regenerative cellular proliferation.

Chloroform is a nongenotoxic-cytotoxic carcinogen in rodents. As such, events related to cytotoxicity are the driving force for cancer induction. In this paper we extended an existing physiologically based pharmacokinetic (PBPK) model for chloroform to describe a plausible mechanism linking the hepatic metabolism of chloroform to hepatocellular killing and regenerative proliferation. The key aspects of this mechanism are (1) the production of damage at a rate proportional to the rate of metabolism predicted by the PBPK model, (2) the saturable repair of the damage, (3) the stimulation of the cell death rate by damage, and (4) the stimulation of the cell division rate as a function of the difference between the control and exposed numbers of cells. This extension allows the simulation of the labeling index and comparison with labeling index data. Data from a previously published chloroform-inhalation study with female B6C3F1 mice that determined cytolethality and regenerative cellular proliferation following exposures of varying concentrations and exposure durations were used for model calibration. Both threshold and low-dose linear linkages between chloroform-induced damage and cell death rate provided visually good fits to the labeling index data after formal optimization of the adjustable parameters, and there was no statistical difference between the fits of the two models to the data. Biologically motivated computational modeling of chloroform-induced cytolethality and regenerative proliferation is a necessary step in the quantitative evaluation of the hypothesis that chloroform-stimulated cell proliferation predicts the rodent tumor response.

Administration, Inhalation↗

Methods for estimating the transfer efficiency of a compressed air spray gun.

The transfer efficiency of a compressed air spray gun is an important performance index with regard to worker health, environmental, and economic considerations. It is defined as the fraction of paint sprayed that coats the surface. Worker exposure has been identified as a function of the transfer efficiency based on total mass of paint sprayed, which can be predicted by a mathematical model developed with nonvolatile oil. This study extends the existing model to include volatile effects by employing a mathematical approach based on a mass balance. This method allows the current model to predict transfer efficiency bounds at two extreme situations: all volatile compounds evaporate either before or after droplet impaction. Model predictions show that tight transfer efficiency bounds are obtained, especially for high values of transfer efficiency. Thus, the average of the upper and lower bounds should be a reasonable estimate of transfer efficiency. It is also found that the current model prediction, which is based on total mass of paint sprayed, for nonvolatile material can be converted to a transfer efficiency based on the mass of solids. The laboratory study shows that the predicted transfer efficiency based on the mass of solids is within the 95 percent C.I. of the measured value. This work relates the transfer efficiency used in industry, which is calculated on the basis of paint solids, with a model that predicts worker exposure during spray painting operations.

Air Movements↗

A field evaluation of the impact of transfer efficiency on worker exposure during spray painting.

This paper presents a mathematical model to predict breathing-zone overspray concentrations produced during spray painting as a function of the overspray generation rate, ventilation and work practices. The overspray generation rate required an estimate of the spray gun transfer efficiency, which was provided by a previously developed mathematical model. These models were evaluated in the field under two different scenarios: first in a controlled environment that approximated the assumptions of models, and then under actual spray painting conditions. Results from the first test showed the model overestimated transfer efficiency, but the measured exposures and predicted exposures were not significantly different. During actual spray painting operations, all task exposures were within a factor of three of the model predictions, and there was no statistical difference between the measured and predicted values. The predicted average exposure of each worker was within the 95% confidence interval. The overall mean exposure was within one standard error of the model prediction. The current study expands on the original exposure model by including a transfer efficiency model to provide a better estimate of the overspray generation rate. The theoretical foundation between exposure and its primary determinants is established, and this knowledge can be applied to design and can evaluate optimal control interventions. Also, the general methodology presented here for developing an exposure model is applicable to operations other than spray painting.

Aerosols↗