BACKGROUND: Because of their size effect, nanometer particles (NPs) can combine molecular within cells, which can result in cell necrosis or apoptosis. But there are no systematic mechanisms of apoptosis induced by NPs about biological safety of NPs.OBJECTIVE: To investigate the effect of nano-hydroxyapatite particles on mononuclear macrophage in rat abdominal cavity at celluar and molecular level.DESIGN, TIME AND SETTING: A materials-cytology observation was performed at Shanghai Biomaterials Research & Testing Center from January 2001 to December 2008.MATERIALS: SD rats of clean grade were provided by SINO-BRITISH SIPPR/BK LAB. ANIMAL Co., Ltd.; NPs were provided by Shanghai Institute of Ceramics.METHODS: Peritoneal fluid was extracted under a sterility environment to in vitro separate and culture mononuclear macrophage using adherence method. The concentration of cell was adjusted at 2×10~9/L. At 300 W/40 kHz ultrasound, cell suspension containing 20,100 and 200 mg/L nano-hydroxyapatite particles was prepared to induce mononuclear macrophage for 24 hours, respectively. A normal control group was established.MAIN OUTCOME MEASURES: Ultrastructural phenotype was detected using transmission electron microscope; apoptotic rate was measured using AnnexinV-EGFP/PI staining; variation of apoptosis-related P53 gene expression was detected using Western Blot.RESULTS: Pseudopodia of mononuclear macrophage in the normal control group were intact, nuclear membrane was normal, and nucleoplasm was uniformed. After inducing by 20,100, 200 mg/L nano-hydroxyapatite particles for 24 hours, apoptotic morphological characteristics were typical in mononuclear macrophage. Compared with normal control group, apoptotic rate was significantly increased following the induction of 20 and 100 mg/L nano-hydroxyapatite (P< 0.01), and the increasing in the 100 mg/L nano-hydroxyapatite particle group was greater than 20 mg/L nano-hydroxyapatite particle group (P < 0.05). P53 protein was not observed in mononuclear macrophage in the normal control group. Following induction of varying concentrations of nano-hydroxyapatite particles, P53 protein expression was increased in the mononuclear macrophage, and the expression was positively related to concentration of nano-hydroxyapatite particles.CONCLUSION: Nano-hydroxyapatite particles can induce p53 expression through phosphorylation, which promotes downstream genes and finally results in cell apoptosis.

This study was aimed to develop a maximum a posteriori Bayesian (MAPB) estimation method to estimate individual pharmacokinetic parameters based on D-optimal sampling strategy. Meanwhile, the performance of MAPB was compared with the multiple linear regression (MLR) method in terms of accuracy and precision. Pharmacokinetic study of pioglitazone was employed as the example case. The population pharmacokinetics was characterized by nonlinear mixed effects model (NONMEM). The sparse sampling strategy (1-4 points) was identified by D-optimal algorithm using WinPOPT software. The simulated data generated by Monte Carlo method were used to access the performance of MAPB and MLR. As the number of samples per subject decreased, the accuracy and precision of MAPB method tended to get worse. The estimation for CL and Vby MAPB using D-optimal two-point design had less bias with low inter-individual variability, and had more bias and imprecision with high residue variability. The estimation of AUC by MAPB using D-optimal 2 points design had similar accuracy and precision to MLR. However, MAPB estimation was better than MLR while adjusting the sampling time to one hour. Overall, the MAPB method had similar predictive performance as MLR, but MAPB could provide more pharmacokinetic information with higher sampling flexibility.

Objective To study the effect of the custom of long term chewing lime tobacco on human tooth enamel electron spin resonance (ESR) dosimetry. Methods A total of 20 enamel samples from lingual parts of adults teeth collected in Bombay, India were obtained by mechanical method. Some enamel samples from Japanese adults were extracted and 10 mixed samples were prepared. Enamel samples were exposed to different doses of 60Co γ-rays several times, and ESR spectra were measured after exposure. Results ESR background signals of 9 Bombay samples were found 1.5-3.3 times higher than those of Japanese mixed samples. The γ-ray dose responses of dosimetric signal with higher background level were a little lower, and the average sensitivity was (0.42 ± 0.03 )mGy, which was close to that of Japanese mixed samples. Conclusions The average level of background signals of Bombay samples was much higher than that of other non-chewing tobacco area, which was possibly caused by tobacco lime, the main component in chewing tobacco productions, and it would help to explore its special influences on ESR, and improve dose reconstruction in accuracy.

The inflammatory response is an essential role of innate immune cells such as neutrophils, which plays an important role in the occurrence and development of inflammatory diseases. Neutrophil extracellular traps (NETs) are responsible for killing microorganisms and inducing the inflammatory response. We review the function of NETs in inflammatory diseases based on research publications since 2016. In addition, the ability of drugs that target NETs to ameliorate inflammation-related diseases is summarized. This review suggests a new strategy of targeting NETs for the treatment of inflammation-related diseases.

OBJECTIVETo study the Cupric ion release characteristics of different copper raw materials in intrauterine device in vitro by ICP. Reveal the relationship between purity and shape of Cu-IUD copper and copper ion release.

METHODSAccording to a certain proportion, the copper raw materials were 100 times diluted into the simulated uterine solution at 37 +/- 0.5 degrees C. Replaced medium at certain time points and collected soaking liquid. Using ICP analyzed the concentration of copper ion released.

RESULTSThe largest daily release of copper ions was in the first 7 days. There was no statistically significant difference between the copper ion release amount of 99.99% and 99.95% purity copper wire (P > 0.05). The release of copper ion of the copper wire was far greater than that of the copper pipe in early stage (P < 0.01). The release amount decreased and stabilized at 56 day.

CONCLUSIONRelease characteristics of copper ion could effectively analysis by ICP. And in the same area, the release amount of copper ions of copper wire was greater than that of copper pipe.

The purpose of this study is to investigate the effects of multiple-trough sampling design and nonlinear mixed effect modeling (NONMEM) algorithm on the estimation of population and individual pharmacokinetic parameters. Oxcarbazepine and tacrolimus were used as one-compartment and two-compartment model drugs, respectively. Seven sampling designs were investigated using various number of trough concentrations per individual ranging from 1-4. Monte Carlo simulations were performed to produce state-steady trough concentrations. One-compartment model was used to fit simulated data from oxcarbazepine and tacrolimus. The accuracy and precision of the estimated parameters were evaluated using the median prediction error (PE), the median absolute PE and boxplot. The results indicated that trough concentrations could yield reliable estimates of apparent clearance (CL/F). For oxcarbazepine, as the number of trough concentrations per subject increased, the accuracy and precision of CL/F, between-subject variability (BSV) of CL/F and residual variability (RUV) tended to be improved. For tacrolimus, however, although no improvement were observed in the accuracy of CL/F and BSV of CL/F, the PE distribution ranges were significantly narrowed and the RUV estimates were less bias and imprecise. In terms of algorithm, Monte Carlo importance sampling (IMP) and IMP assisted by mode a posteriori estimation (IMPMAP) were consistently better than other methods. Additionally, the sampling design had no significant effects on the individual parameter estimates, which were only depended on the interaction between BSV and RUV in various algorithms. Decreased in BSV and RUV levels can improve the accuracy and precision of the estimation for both population and individual pharmacokinetic parameter estimates.
Algorithms ; Bayes Theorem ; Carbamazepine ; analogs & derivatives ; pharmacokinetics ; Humans ; Immunosuppressive Agents ; pharmacokinetics ; Models, Biological ; Monte Carlo Method ; Nonlinear Dynamics ; Regression Analysis ; Tacrolimus ; pharmacokinetics

The purpose of this study is to investigate the effects of multiple-trough sampling design and nonlinear mixed effect modeling (NONMEM) algorithm on the estimation of population and individual pharmacokinetic parameters. Oxcarbazepine and tacrolimus were used as one-compartment and two-compartment model drugs, respectively. Seven sampling designs were investigated using various number of trough concentrations per individual ranging from 1-4. Monte Carlo simulations were performed to produce state-steady trough concentrations. One-compartment model was used to fit simulated data from oxcarbazepine and tacrolimus. The accuracy and precision of the estimated parameters were evaluated using the median prediction error (PE), the median absolute PE and boxplot. The results indicated that trough concentrations could yield reliable estimates of apparent clearance (CL/F). For oxcarbazepine, as the number of trough concentrations per subject increased, the accuracy and precision of CL/F, between-subject variability (BSV) of CL/F and residual variability (RUV) tended to be improved. For tacrolimus, however, although no improvement were observed in the accuracy of CL/F and BSV of CL/F, the PE distribution ranges were significantly narrowed and the RUV estimates were less bias and imprecise. In terms of algorithm, Monte Carlo importance sampling (IMP) and IMP assisted by mode a posteriori estimation (IMPMAP) were consistently better than other methods. Additionally, the sampling design had no significant effects on the individual parameter estimates, which were only depended on the interaction between BSV and RUV in various algorithms. Decreased in BSV and RUV levels can improve the accuracy and precision of the estimation for both population and individual pharmacokinetic parameter estimates.

Objectlve To study the properties of goat tooth enamel electron spin resonance (ESR)dosimetry.Methods Tootll enamel samples of goats were achieved by combined mechanical and chemical treatment at the ages of l,2,3,5,and 6 years.respectively and 9 enamel samples of adult molar were obtained.These enamel samples were exposed to 137Cs γ-rays at the cumulative doses of 0,0.5,1.0,2.0,and 5.0 Gy,respectively.ESR spectra Was measured before and after exposure.Results The background signal of goat tooth samples W88 21.5,significantly lower than that of the adult molar samples(39.5).The dusimetric signal intensity of the goat enamel increased with the radiation dose in a linear manner just as that of the human molars.The average radiation sensitivity of the goat tooth samples was(34.3±1.9)/Gy,close to that of the human tooth samples.Conclusions Goat teeth can be used for retrospective radiation dose reconstruction when human teeth are unavailable,in order to previde scientific data for dose reconstruction accurately.

Objective To investigate solar radiation and its effects on human tooth enamel electron spin resonance (ESR) dosimetry. Methods 11 tooth enamel samples were prepared by mechanical method. The intensity of solar iUuminanee was measured with a light meter, the measured illuminance was converted to insolation using a coefficient. Summation of solar radiation was evaluated. Enamel samples were exposed to 60 Co γ rays followed by sunlight on sunny days, and ESR spectra were scanned after different exposure. Results The solar radiation to the samples was (580 ± 16) MJ/m2. Solar exposure also caused dosimetrie signal. The perpendicular component of dosimetrie signal increased linearly with the amount of solar radiation, another signal close to background tended to saturation. Conclusions The average effect of the solar radiation on the signal was be used to recognize the effect of solar radiation on the enamel, and estimate external dose accurately.

Objective To determine the surfactant protein A (SP-A) subtype distribution and expression in human renal tissue and cultured human renal tubular epithelial cells(HK-2), and to explore the influence of Lipopolysaccharide (LPS) on the expression of SP-A subtypes mRNA and SP-A protein. Methods lmmunohistochemical staining was performed using SP-A polyclonal antibodies. RT-PCR was performed with mRNA from HK-2 cells and normal human kidney.Restriction fragment length polymorphism(RFLP) and sequencing were used to evaluate the subtypes of SP-A. The relative content of SP-A mRNA in human kidney and human lung was compared by real-time PCR. Western blotting analysis for SP-A was performed on protein from renal tissue and cultured HK-2 cells SP-A protein in human urine and culture supernatant of HK-2 cells was measured by enzyme-linked immunosorbent assay (ELISA) and Western blotting respectively. HK-2cells were treated with LPS at various concentrations (0,0.1,1,2,5,10 mg/L) for 8 h and at 5mg/L for various time points (0,2,4,8,16,24 h). Expression of SP-A mRNA and protein was analyzed by RT-PCR and Western blotting. Results SP-A was localized in renal tubular epithelial cells of both proximal and distal convoluted tubules. SP-A1, SP-A2 mRNA and protein could be detected in normal HK-2 cells and human kidney. The significant secretion of SP-A [urine: (106.614172.772) nmol/L, n=30; culture supernatant: (85.533±58.622) nmol/L, n=10] was shown. The levels of SP-A1, SP-A2 mRNA and Sp-A protein in HK-2 cells were significantly decreased after treatment with LPS. Conclusions Human renal tubular epithelial cells can express both SP-A1 and SP-A2 genes which may play an important role in inflammation modulation of kidney.