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1.
Acta Pharmaceutica Sinica ; (12): 265-271, 2020.
Article in Chinese | WPRIM | ID: wpr-789029

ABSTRACT

Uranium [U(Ⅵ)] in the blood is known to form stable complexes with apotransferrin (apo-Tf), which plays an important role in mediating the cytotoxicity induced by U(Ⅵ) transported to cells. The present study aimed to establish an new in vitro screening model of U(Ⅵ) decorporation agents through exploring the capability of chelating agents competing with U(Ⅵ) binding to apo-transferrin based on enzyme-linked immunosorbent assay (ELISA). The optimal concentrations of apo-Tf coated antigen, Tf antibody, secondary antibody and U(Ⅵ) treatment were achieved and the stability and reproducibility of this method were validated by methodology study. Using this model, the ability of four chelating agents to mobilize the U(Ⅵ) binding to apo-Tf was evaluated, and the rank of competitiveness was catechol-3,6-bis(methyleiminodiacetic acid) (CBMIDA) ≈ Tiron > apo-Tf > DTPA-CaNa3 ≈ DTPA-ZnNa3. The efficacy of these chelating agents in removal of U(Ⅵ) was tested by animal experiments. The results showed that immediate administration of CBMIDA or Tiron after injection of U(Ⅵ) in mice significantly promoted urinary U(Ⅵ) excretion and reduced U(Ⅵ) accumulation in kidneys and femurs, while DTPA-CaNa3 and DTPA-ZnNa3 have no obvious effects as compared to U(Ⅵ)-exposed mice alone, which was consistent with the results of competitive ELISA method. The animal experiments conform to the rules of the Animal Research Ethics Committee of School of Pharmacy of Fudan University. These results show that the new proposed method is rapid, simple and convenient with good reproducibility and has the potential to be used for in vitro screening of U(Ⅵ) decorporation agents.

2.
Fudan University Journal of Medical Sciences ; (6): 674-679, 2017.
Article in Chinese | WPRIM | ID: wpr-662151

ABSTRACT

Objective To investigate the cognition and attitude towards free pneumonia vaccination among elderly people aged over 60 years old in Minhang District of Shanghai.Methods Target population was based on registered citizen over 60 years old in Minhang District.According to their willingness of pneumonia vaccineinjection,participants were divided into two groups,willing group and refused group.We randomly selected 910 people for each group.And before vaccination,a self-made "pneumonia vaccination behavior cognition and attitude questionnaire" was completed by each participant.Whether there were significant differences in the cognitive and attitude towards pneumonia vaccination between the two groups was analyzed by t test.x2 test and Logistic regression model was used to analyze main risk factors affecting the elderly attitude and behavior towards pneumonia vaccination.Results Statistical significant relations were found among following five cognition dimensions,which were benefits of vaccination (t =21.691,P<0.01),values of vaccination (t =6.105,P<0.01),the severity of affecting pneumonia (t =9.882,P<0.01),vulnerable of getting pneumonia (t =5.670,P<0.01) and obstacle towards vaccination (t =-7.114,P<0.01).x2 test and Logistic regression analysis results suggested that among these five dimensions,cognition of vaccination benefits (B =0.610,P<0.01) played the most important role in the attitude of elderly people between the two groups.The severity of affecting pneumonia (B =-0.452,P<0.01) and obstacle towards vaccination (B =0.311,P<0.01) played less important role regards elderly making decision of taking pneumonia vaccination.There was no statistically significant relations in sensitivity of getting pneumonia.In addition to the five dimensions discussed above,people who are engaged in commercial and service industry before retirement,with an annual income of between ten thousand to one hundred thousand and having chronic diseases are more likely to have a higher degree of acceptance of taking pneumonia vaccine than those without these properties.Conclusions There were significantly differences in cognitive behavior between willing to injection group and refused group among elderly.The results suggest that the benefits of pneumonia vaccination in older people with chronic diseases may have a positive effect on further increasing the rate of free pneumonia vaccination in the elderly population in Minhang District of Shanghai.

3.
Fudan University Journal of Medical Sciences ; (6): 674-679, 2017.
Article in Chinese | WPRIM | ID: wpr-659485

ABSTRACT

Objective To investigate the cognition and attitude towards free pneumonia vaccination among elderly people aged over 60 years old in Minhang District of Shanghai.Methods Target population was based on registered citizen over 60 years old in Minhang District.According to their willingness of pneumonia vaccineinjection,participants were divided into two groups,willing group and refused group.We randomly selected 910 people for each group.And before vaccination,a self-made "pneumonia vaccination behavior cognition and attitude questionnaire" was completed by each participant.Whether there were significant differences in the cognitive and attitude towards pneumonia vaccination between the two groups was analyzed by t test.x2 test and Logistic regression model was used to analyze main risk factors affecting the elderly attitude and behavior towards pneumonia vaccination.Results Statistical significant relations were found among following five cognition dimensions,which were benefits of vaccination (t =21.691,P<0.01),values of vaccination (t =6.105,P<0.01),the severity of affecting pneumonia (t =9.882,P<0.01),vulnerable of getting pneumonia (t =5.670,P<0.01) and obstacle towards vaccination (t =-7.114,P<0.01).x2 test and Logistic regression analysis results suggested that among these five dimensions,cognition of vaccination benefits (B =0.610,P<0.01) played the most important role in the attitude of elderly people between the two groups.The severity of affecting pneumonia (B =-0.452,P<0.01) and obstacle towards vaccination (B =0.311,P<0.01) played less important role regards elderly making decision of taking pneumonia vaccination.There was no statistically significant relations in sensitivity of getting pneumonia.In addition to the five dimensions discussed above,people who are engaged in commercial and service industry before retirement,with an annual income of between ten thousand to one hundred thousand and having chronic diseases are more likely to have a higher degree of acceptance of taking pneumonia vaccine than those without these properties.Conclusions There were significantly differences in cognitive behavior between willing to injection group and refused group among elderly.The results suggest that the benefits of pneumonia vaccination in older people with chronic diseases may have a positive effect on further increasing the rate of free pneumonia vaccination in the elderly population in Minhang District of Shanghai.

4.
China Occupational Medicine ; (6): 525-530, 2016.
Article in Chinese | WPRIM | ID: wpr-876981

ABSTRACT

OBJECTIVE: To screen small molecule metabolites of dibutyl phthalate( DBP) in the rat plasma using ~1H nuclear magnetic resonance( NMR) technology; and to clarify the changes of metabolites and possible mechanism in metabolic regulation of DBP in rats from the molecular level and the aspects of material and energy metabolism. METHODS: According to random number table method,twenty-four specific pathogen free SD male rats were divided into four groups: control group,low dose group,middle dose group and high dose group with the given dose of 0,500,1 000 and1 500 mg / kg of body mass,respectively. After giving DBP of gavage once a day for two weeks,the plasma samples were obtained,and ~1H NMR spectra was recorded. The plasma metabonomic profiles were analyzed using pattern recognition.Difference metabolites were screened by principal components analysis,partial least squares-discriminate analysis and orthogonal partial least squares-discriminate analysis. Biomarkers was screened by variable importance in the projection norm. RESULTS: There were changes of twelve important metabolites in the plasma metabonomic profiles between DBP treatment groups and control group. The differences of metabolites had dose-effect relationship. Plasma levels of high density lipoprotein cholesterol, low density lipoprotein cholesterol, hydrobutyrate, glycoprotein, citric acid, glucose,creatine phosphate,unsaturated fatty acid,tyrosine and phenylalanine were reduced( P < 0. 05),while lactic acid and pyruvic acid were increased( P < 0. 05). CONCLUSION: DBP induces the metabolic disorders including amino acid metabolism,lipid metabolism and energy metabolism.

5.
Acta Pharmaceutica Sinica ; (12): 1308-1313, 2011.
Article in Chinese | WPRIM | ID: wpr-232993

ABSTRACT

This study is to assess the efficacy of BPCBG on the decorporation of uranium (VI) and protecting human renal proximal tubular epithelial cells (HK-2) against uranium-induced damage. BPCBG at different doses was injected intramuscularly to male SD rats immediately after a single intraperitoneal injection of UO2(CH3COO)2. Twenty-four hours later uranium contents in urine, kidneys and femurs were measured by ICP-MS. After HK-2 cells were exposed to UO2(CH3COO)2 immediately or for 24 h followed by BPCBG treatment at different doses for another 24 or 48 h, the uranium contents in HK-2 cells were measured by ICP-MS, the cell survival was assayed by cell counting kit-8 assay, formation of micronuclei was determined by the cytokinesis-block (CB) micronucleus assay and the production of intracellular reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA) oxidation. DTPA-CaNa3 was used as control. It was found that BPCBG at dosages of 60, 120, and 600 micromol kg(-1) resulted in 37%-61% increase in 24 h-urinary uranium excretion, and significantly decreased the amount of uranium retention in kidney and bone to 41%-31% and 86%-42% of uranium-treated group, respectively. After HK-2 cells that had been pre-treated with UO2(CH3COO)2 for 24 h were treated with the chelators for another 24 h, 55%-60% of the intracellular uranium was removed by 10-250 micromol L(-1) of BPCBG. Treatment of uranium-treated HK-2 cells with BPCBG significantly enhanced the cell survival, decreased the formation of micronuclei and inhibited the production of intracellular ROS. Although DTPA-CaNa3 markedly reduced the uranium retention in kidney of rats and HK-2 cells, its efficacy of uranium removal from body was significantly lower than that of BPCBG and it could not protect uranium-induced cell damage. It can be concluded that BPCBG effectively decorporated the uranium from UO2(CH3COO)2-treated rats and HK-2 cells, which was better than DTPA-CaNa3. It could also scavenge the uranium-induced intracellular ROS and protect against the uranium-induced cell damage. BPCBG is worth further investigation.


Subject(s)
Animals , Humans , Male , Rats , Cell Line , Cell Survival , Chelating Agents , Chemistry , Pharmacology , Dose-Response Relationship, Drug , Epithelial Cells , Cell Biology , Metabolism , Kidney , Metabolism , Kidney Tubules, Proximal , Cell Biology , Micronucleus Tests , Molecular Structure , Organometallic Compounds , Toxicity , Random Allocation , Rats, Sprague-Dawley , Reactive Oxygen Species , Metabolism , Uranium , Metabolism , Urine
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