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Toll-like receptors (TLRs), the triggers of the innate and adaptive immune responses, are involved in the pathogenesis of type 2 diabetes mellitus (T2DM). Several studies have investigated the effects of genetic polymorphisms in TLR4 and TLR2, but they have yielded limited results. We investigated whether non-missense genetic polymorphisms in the regulatory regions of TLR4 and TLR2 were related to T2DM in a southern Chinese population. Single nucleotide polymorphisms (SNPs) in TLR4 (rs1927911, rs11536889, rs1927907, rs1927906, rs1927914, rs7873784, and rs2149356) and TLR2 (rs1898830, rs3804099, rs4696480, and rs3804100) were genotyped in 552 T2DM and 552 unrelated age- and gender-matched controls by SNaPShot Multiplex assay. Genotypes GG (OR = 0.09, 95%CI = 0.01- 0.83, P = 0.03) and CG (OR = 0.08, 95%CI = 0.01-0.74, P = 0.03) of the 3'-untranslated region (UTR) SNP rs7873784 in TLR4, and genotype AG (OR = 0.67, 95%CI = 0.46-0.97, P = 0.04) and allele G (OR = 0.88, 95%CI = 0.79-0.97, P = 0.01) of the intron SNP rs1898830 in TLR2 were identified as protective against the development of T2DM in southern Chinese people. In contrast, a meta-analysis of rs1927911 and rs1927914 showed no association. Haplotypes AGTT (OR = 0.34, 95%CI = 0.15-0.77, P = 0.01) and AATT (OR = 1.20, 95%CI = 1.01- 1.44, P = 0.05) in TLR2 were significantly associated with susceptibility to T2DM. Our results suggest that the effects of non-missense polymorphisms located in the regulatory regions of TLR4 and TLR2 should not be neglected in T2DM association analysis.

This study was conducted to investigate the methodology and feasibility of developing a portable x-ray fluorescence (XRF) technology to quantify lead (Pb) in bone in vivo. A portable XRF device was set up and optimal settings of voltage, current, and filter combination for bone lead quantification were selected to achieve the lowest detection limit. The minimum radiation dose delivered to the subject was calculated by Monte Carlo simulations. An ultrasound device was used to measure soft tissue thickness to account for signal attenuation, and an alternative method to obtain soft tissue thickness from the XRF spectrum was developed and shown to be equivalent to the ultrasound measurements (intraclass correlation coefficient, ICC = 0.82). We tested the correlation of in vivo bone lead concentrations between the standard KXRF technology and the portable XRF technology. There was a significant correlation between the bone lead concentrations obtained from the standard KXRF technology and those obtained from the portable XRF technology (ICC = 0.65). The detection limit for the portable XRF device was about 8.4 ppm with 2 mm soft tissue thickness. The entrance skin dose delivered to the human subject was about 13 mSv and the total body effective dose was about 1.5 µSv and should pose minimal radiation risk. In conclusion, portable XRF technology can be used for in vivo bone lead measurement with sensitivity comparable to the KXRF technology and good correlation with KXRF measurements.

In the present paper, nitrate and nitrite in foodstuffs and saliva were simultaneously determined using a non-suppressed ion chromatography (IC) method with a bulk acoustic wave sensor (BAW) as detector, and 1.5 mmol/L potassium hydrogenphthalate (KHP) as mobile phase. The IC-BAW method is simple, rapid and accurate. The determination limits for nitrite and nitrate are 0.20 and 0.30 mg/L, respectively. The IC-BAW is comparable and agrees with the conventional spectrophotometric method for nitrite and nitrate determination.

A novel method, equilibrium dialysis/piezoelectric quartz crystal sensor, applied to determine the binding parameters of diethyldithiocarbamate to human plasma protein is proposed. Based on the investigation of the equilibrium reaction for the binding of drug to protein, the related theoretical equations for this binding were derived. By monitoring the frequency responses of a copper-plated piezoelectric quartz crystal sensor to drug in and out of a dialysis membrane after equilibrium, the binding parameters were determined, i.e., 0.375 micromol g(-1) for beta(p), 6.496 microM for K(dp), 141.99 L mmol(-1) for K(p), and 0.043 for N. These values were in good agreement with reference values. It was found that this method may have application for studying the characteristics of the interaction between other drugs and proteins., (Copyright 2000 Academic Press.)

In the present paper, determination of Na+, K+ and NH4+ in saliva and serum was carried out using an ion chromatography (IC) method with a bulk acoustic wave (BAW) sensor as detector and 2.0 mmol/l nitric acid as mobile phase. The IC-BAW method is simple, rapid and accurate. Comparison between the BAW detector and the conventional conductivity detector (CDD) was discussed. The IC-BAW showed agreement with the commonly used flame photometric method for Na+ and K+ and enzymatic method for NH4+, as well as IC-CDD for those three cations.

A simple and sensitive extraction-gravimetric method for the determination of dipyridamole is presented. The method is based on the extraction of free dipyridamole with chloroform, after neutralization with a basic agent, followed by measurement of the frequency shift response of the specially designed surface acoustic wave resonator sensor after evaporation of the extractant from the surface of the resonator. The frequency shift response was proportional to the amount of dipyridamole in the range 0.065-1.12 micrograms. Experimental parameters and the effect of interfering substances on the assay of dipyridamole were also examined in this study. The method was applied to the determination of dipyridamole in tablets.

A method of using a bulk acoustic wave (BAW) device to study the hemorheological phenomena is proposed. By measuring the resonant resistance of a BAW device, the dependence of the plasma viscosity on its composition is investigated. It has been found that during the process of the plasma coagulation, the frequency response of a BAW device is dominated by the change in plasma viscoelasticity, and useful information such as the coagulation time and the viscoelasticity of coagulated plasma can be obtained from the curve of frequency response. Based on the BAW quartz detection system, effects of fibrinogen, thrombin and some drugs on the plasma coagulation are investigated. The results show that the BAW device based on the oscillator method possesses some advantages, such as high sensitivity, simplicity of use, cost effectiveness and small sample volume for clinical hemorheological study.

A new analytical technique for the assay of pharmaceutical substances at low concentration levels has been proposed and applied to the determination of vitamin C as an example of its application. It is based on the chemical reaction of vitamin C with iodine in a sodium citrate-hydrochloric acid medium, followed by measurement of the frequency change of a silver-plated piezoelectric quartz crystal. The frequency change is proportional to the vitamin C concentration from 2 x 10(-7) to 4 x 10(-6) M. The method was applied to the assay of vitamin C in pharmaceutical preparations.

According to the response properties of piezoelectric crystal quartz sensors to the solution conductivity the frequency shift response was derived to show a linear dependence on the concentrations of vitamin B1 (VB1) and vitamin C (VC). This was experimentally verified and a calibration model for simultaneous determinations of the two vitamins was established. The usefulness of the technique was evaluated by quantitation of mixtures of unknown composition using common multiple linear regression (MLR) and partial least squares (PLS). The average relative standard deviations for six samples were 4.46% for VB1 and 6.63% for VC with MLR; and 1.97% for VB1 and 2.74% for VC with PLS, respectively.

The transfer phenomena of quinine drug at the aqueous 1,2-dichloroethane (DCE) interface have been studied by the current-scanning polarography. The relationships between the wave height and pH of aqueous phase, concentration of quinine as well as the rate of water drop are discussed. The effect of supporting electrolyte, buffer solution and the nature of organic solvent on the polarographic wave is studied. The transfer characteristics of quinine in aqueous phase and in organic phase are compared. The mono-protonated and diprotonated quinines can both transfer at the interface so as to produce two polarographic waves. The transfer process of quinine at the interface is simultaneously controlled by diffusion and reestablishment of the disturbed protonated equilibrium of quinine. A further investigation is made by chronopotentiometry. On the basis of the theoretical analysis, the formulae of the limiting current are derived and discussed. The theoretical results are in agreement with the experimental ones. The transfer mechanism of quinine is put forward.

A new extraction--frequency metric method has been proposed for the determination of ephedrine, which can not be determined by the conventional extraction--weighing method due to its volatility. The method is based on extraction of the free alkaloid followed by measuring the frequency shift of a specially constructed ring--coated piezoelectric crystal at room temperature. The frequency shift is in linear relationship with the content of ephedrine hydrochloride over a range 0.05-1.2 micrograms with a correlation coefficient of 0.999 and a detection limit of 0.02 micrograms. Methods for the assay of ephedrine hydrochloride tablet and nasal solution have been proposed.

A new measurement technique has been proposed and applied to the determination of chlorpheniramine as an example of its application. It is based on the extraction of free chlorpheniramine into carbon tetrachloride after neutralization with a basic agent, followed by measurement of the frequency change of the specially designed ring-coated piezoelectric sensor after evaporation of the extractant from the crystal surface. The frequency change is proportional to the chlorpheniramine amount in the range 0.025-1.2 microgram. The method has been applied to the determination of chlorpheniramine maleate in pharmaceutical preparations.

A new type of MCCS (microcells connected in series) has been constructed and its performances investigated. It has been applied to the determination of streptomycin. The sensitivity and accuracy have been increased significantly. A theoretical model for the error of determination using the MCCS has been suggested and proved experimentally using the Monte Carlo method, and the error model proposed in Ref. [1] revised.

A new method for the rapid determination of microgram and submicrogram amounts of pentoxyverine citrate has been suggested using a ring-coated piezoelectric quartz crystal in combination with the neutralization extraction technique. The detection limit is 0.02 microgram. Frequency shift is directly proportional to the pentoxyverine citrate concentration in the range of 0.05-1.6 micrograms, with a correlation coefficient of 0.999 and a coefficient of variation of 2.3%. The new method suggests a number of advantages over the classical neutralization-extraction method.

Drug ion-selective electrodes made with hetero-poly anion as exchange site exhibit better performances than the respective electrodes of conventional tetraphenylboron type, yielding low detection limits and fast responses. Functions of propantheline, berberine, dibazol, thiamine, streptomycin, moroxydine, tetracycline, oxytetracycline, doxycycline, erythromycin, carbetapentane, benzydamine, tetramisole and trifluoperazine electrodes are reported. The electrodes can be used in potentiometric determinations of the respective drugs in aqueous solutions, urine and mixture of water and organic solvents.