2002 Vol. 15, No. 3

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Zinc In CCl4 Toxicity
2002, 15(3): 187-195.
Objective To investigate the protective effect of zinc in CCl4-induced hepatotoxicity. Methods Rats were treated with zinc acetate for four days. The zinc doses were 5 mg Zn/kg and 10 mg Zn/kg body weight respectively. Two groups of the zinc acetate-treated rats were later challenged with a single dose of CCl4 (1.5 mL/kg body weight). Results Compared to control animals, the plasma of rats treated with CCl4 showed hyperbilirubinaemia, hypoglycaemia, hypercreatinaemia and hypoproteinaemia. When the animals were however supplemented with zinc in form of zinc acetate before being dosed with CCl4, the 5 mg Zn/kg body weight of zinc acetate reversed the hypoproteinaemia induced by CCl4, whereas the 10mg Zn/kg body weight of zinc acetate reversed the hypoglycaemia, hyperbilimbinaemia and hypercreatinaemia induced by CCl4. Conclusion The 10mug Zn/kg body weight of zinc acetate is more consistent in protecting against CCl4 hepatotoxicity. The possible mechanisms of protection are highlighted.
Effect of Micronutrient Supplementation on the Growth of Preschool Children in China
2002, 15(3): 196-202.
Objective To study the relationship between micronutrient supplementation and children growth. Methods A double-blind, placebo-controlled trial was conducted in 156 growth retarded preschool children. They were randomly assigned to five groups: supplemental control (S-control,n=28), zinc supplementation(+Zn, 3.5mg Zn/day, n=34), zinc and calcium supplementation (+ZnCa,3.5mg Zn+250mg Ca/day, n=37), zinc and calcium and vitamin A supplementation (+ZnCaVA,3.5mgZn +250mgCa+200gVA/day, n=28), Calcium and vitamin A supplementation (+CaVA,250mgCa + 200gVA/day, n=29). Another 34 children with normal height were selected as normal control (N-control). Supplementation continued for twelve months. Results The height gain in +Zn group (7.84cm per year) and +ZnCa group (7.70 cm per year) was significantly higher than that in S-control group (6.74 cm per year, P<0.05); The weight gain in +ZnCaVA group (2.55kg per year)and +CaVA group (2.57 kg per year) was also significantly higher than that in S-control group (2.19kg per year, P<0.05); The average days of illness in each supplementation group were lower than that in S-control (13 days per year compared with 23 days per year). No significant difference was observed on bone age. Conclusion Zinc and Zinc+Calcium supplementation can improve the height gain,and vitamin A can improve weight gain in growth retarded preschool children, but do not affect the maturity of bone. Micronutrient supplementation can lower the morbidity of these children.
Randomized Terminal Linker-dependent PCR: A Versatile and Sensitive Method for Detection of DNA Damage
ZHANG ZHI-WEI, Heng Zheng-chang
2002, 15(3): 203-208.
Objective To design and develop a novel, sensitive and versatile method for in vivo foot printing and studies of DNA damage, such as DNA adducts and strand breaks. Methods Starting with mammalian genomic DNA, single-stranded products were made by repeated primer extension, these products were ligated to a double-stranded linker having a randomized 3′ overhang, and used for PCR.DNA breaks in p53 gene produced by restriction endonuclease AfaI were detected by using this new method followed by Southern hybridization with DIG-labeled probe. Results This randomized terminal linker-dependent PCR (RDPCR) method could generate band signals many-fold stronger than conventional ligation-mediated PCR (LMPCR), and it was more rapid, convenient and accurate than the terminal transferase-dependent PCR (TDPCR). Conclusion DNA strand breakage can be detected sensitively in the gene level by RDPCR. Any lesion that blocks primer extension should be detectable.
Impact of Long-term Exposure to Air Particulate Matter on Life Expectancy and Survival Rate of Shanghai Residents
2002, 15(3): 209-214.
Objective To evaluate the impact of long-term air particulate matter exposure on the life expectancy and survival rate of Shanghai residents. Methods Epidemiology - based exposureresponse function was used for the calculation of attributable deaths to air particulate matter in Shanghai, and the effect of long-term exposure to particulate matter on life expectancy and survival rate was estimated using the life table of Shanghai residents in 1999. Results It was shown that in 1999, the long-term air particulate matter exposure caused 1.34-1.69 years reduction of life expectancy and a decrease of survival rate for each age group of Shanghai residents. Conclusion The effect of long-term exposure to air particulate matter on life expectancy is substantial in Shanghai.
Silica Induced Early Fibrogenic Reaction in Lung of Mice Ameliorated by Nyctanthes arbortristis Extract
2002, 15(3): 215-222.
Objective To investigate the pharmacological effect of Nyctanthes arbortristis (NAT) leaf extract in the prevention of lung injury induced by silica particles. Method Lung injury was induced in Swiss mice through inhalation exposure to silica particles (<5μ) using a Flow Past Nose Only Inhalation Chamber at the rate of -10 mg/m3 respirable mass for 5 h. Lung bronchoalveolar lavage (BAL) fluid collected between 48 and 72 h was subjected to protein profiling by electrophoresis and cytokine evaluation by solid phase sandwich ELISA. Lung histopathology was performed to evaluate lung injury. Results Inhalation of silica increased the level of tumor necrosis factor-α(TNF-α), and of the 66 and 63 kDa peptides in the BAL fluid in comparison to sham-treated control. Pre-treatment of silica exposed mice with NAT leaf extract significantly prevented the accumulation of TNF-α in the BAL fluid, but the 66 and 63 kDa peptides remained unchanged. The extract was also effective in the prevention of silica-induced early fibrogenic reactions like congestion, edema and infiltration of nucleated cells in the interstitial alveolar spaces, and thickening of alveolar septa in mouse lung. Conclusion NAT leaf extract helps in bypassing silica induced initial lung injury in mice.
Redifferentiation of Human Gastric Cancer Cells Induced by Ascorbic Acid and Sodium Selenite
ZHENG Qiu-sheng, SUN Xi-ling, WANG Chang-hai
2002, 15(3): 223-232.
Objective To explore the effects and mechanisms of ascorbic acid (AA) and sodium selenite (SS) on growth inhibition and redifferentiation in human gastric cancer cells. Methods In the present study, trypan blue dye exclusion method was used to determine the cell growth curve and mitotic index, cell electrophoresis and colonogenic potential were used as the indexes of redifferentiation. In order to find out the mechanisms of redifferentiation, the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) were assayed, the content of malondialdehyde (MDA), reduced glutathione (GSH) and H2O2 were evaluated. Results After treatment with AA 3 mol/L + SS 2μmol/L, the growth rate and mitotic index of human gastric cancer cells (MGc-803) decreased remarkably. The indexes related with cell malignancy were alleviated. For example, cell surface charge was obviously decreased, the electrophoresis rate was dropped from 2.21 to 1.15μm@s-1@V-1@cm-1. The indexes related with cell redifferentiation were promoted. For example, the colonogenic potential was decreased to 93.5%. These results indicated that redifferentiation of human gastric cancer cells was successfully induced by AA + SS. The activities of SOD and GPX were significantly higher, while the activity of CAT was slower in treated group than that in the control. The content of MDA was slightly decreased, GSH was sharply decreased, and H2O2 content was dramatically increased. Conclusion These results indicated that combination of ascorbic acid and sodium selenite may induce the redifferentiation of human gastric cancer cells and inhibit cell growth by virtue of enhancing the activities of antioxidative enzymes and inducing the formation of H2O2, and altering the cell redox status. Combination of ascorbic acid and sodium selenite may be a potent anticancer agent for human gastric cancer.
Abnormal Reactions of Free Radicals and Oxidative Damages in the Bodies of Patients With Chronic Glomerulonephritis
2002, 15(3): 233-244.
Objective To study the abnormal reactions of a series of free radicals and the oxidative damages induced by free radical abnormal reactions in the bodies of patients with chronic glomerulonephritis. Methods Eighty chronic glomerulonephritis patients (CGNP) and eighty healthy adult volunteers (HAV) were enrolled in a random control study, in which concentrations of nitric oxide (NO) in plasma, lipoperoxides (LPO) in plasma and in erythrocytes, and vitamin C (VC),vitamin E (VE) and beta-carotene (β-CAR) in plasma as well as activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in erythrocytes were determined with spectrophotometric assays. Results Compared with the average values of the above biochemical parameters in the HAV group, the average values of NO in plasma, and LPO in plasma and erythrocytes in the CGNP group were significantly increased (P = 0.0001), while those of VC, VE and β-CAR in plasma as well as those of SOD, CAT and GPX in erythrocytes in the CGNP group were significantly decreased (P = 0.0001). Pearson product-moment correlation analysis showed that with increase of the concentration of blood creatinine as well as prolongation of the course of disease in the CGNP, the concentrations of NO in plasma, and LPO in plasma and erythrocytes in the CGNP increased gradually, while the concentrations of VC, VE and β-CAR in plasma as well as the activities of SOD, CAT and GPX in erythrocytes in the CGNP decreased gradually (P = 0.002454 - 0.000001).The relative risk ratio (RR) of the above biochemical parameters reflecting oxidative damages in the bodies of CGNP ranged from 6.061 to 72.429. The reliability coefficient (alpha) that the above biochemical parameters were used to reflect the oxidative damages of the CGNP was 0.8137,standardized item alpha = 0.9728, Hotelling's T-Squared = 1135680.191, F = 53274.6478, P =0.000001. Conclusions The findings irt this study show that in the bodies of CGNP a series of free radical chain reactions result in severe pathological aggravation and induce oxidative damages in their bodies. Therefore, suitable dose of antioxidants should be supplemented to them so as to alleviate oxidative damages in their bodies.
Effect of Body Mass Index on All-cause Mortality and Incidence of Cardiovascular Diseases - Report for Meta-Analysis of Prospective Studies on Optimal Cut-off Points of Body Mass Index in Chinese Adults
ZHOU Bei-fan
2002, 15(3): 245-252.
Objective To verify the optimal cut-off points for overweight and obesity in Chinese adults based on the relationship of baseline body mass index (BMI) to all-cause mortality, and incidence of cardiovascular diseases from pooled data of Chinese cohorts. Methods The prospective study data of existing cohort studies in China were collected, and the age-adjusted all-cause mortality stratified by BMI were estimated. The similar analysis was repeated after excluding deaths within the first three years of follow-up and after excluding smokers. The incidence of age-adjusted coronary heart disease (CHD) and stroke stratified by BMI were also analyzed. Multiple Cox regression coefficients of BMI for the incidence of CHD and stroke after controlling other risk factors were pooled utilizing the methods of weighting by inverse of variance to reveal whether BMI had independent effect and its strength on the incidence of CHD and stroke. Results The data of 4 cohorts including 76 227persons, with 745 346 person-years of follow-up were collected and analyzed. The age-adjusted allcause mortality stratified by BMI showed a U-shaped curve, even after excluding deaths within the first three years of follow-up and excluding smokers. Age-adjusted all-cause mortality increased when BMI was lower than 18.5 and higher than 28. The incidence of CHD and stroke, especially ishemic stroke increased with increasing BMI, this was consistent with parallel increasing of risk factors. Cox regression analysis showed that BMI was an independent risk factor for both CHD and stroke. Each amount of 2 kg/m2 increase in baseline BMI might cause 15.4%, 6.1% and 18.8 % increase in relative risk of CHD, total stroke and ischemic stroke. Reduction of BMI to under 24 might prevent the incidence of CHD by 11% and that of stroke by15 % for men, and 22 % of both diseases for women. Conclusion BMI ≤18.5, 24-27.9 and ≥28 (kg/m2) is the appropriate cut-off points for underweight, overweight and obesity in Chinese adults.
Polymorphism of Glutathione S-transferase T1, M1 and P1 Genes in a Shanghai Population: Patients With Occupational or Non-occupational Bladder Cancer
2002, 15(3): 253-260.
Objective Glutathione S-transferases are involved in the conjugation of xenobiotics. To explore whether GSTs polymorphisms are involved in the development of occupational or non-occupational bladder cancer, polymorphism frequencies of GSTT1, M1 and P1 were investigated in a normal population, which had been settled in a rural area in Shanghai suburb for at least 5 generations as well as in a group of patients with benzidine exposure related occupational bladder cancer in Shanghai dyestuff industry and a group of patients with non-occupational bladder cancer. Methods PCR based procedures were performed in the study populations to confirm the genotypes of GSTT1, M1 and P1. Results The polymorphisms at locus of GSTP1- A1578G in the normal population differed significantly from those in Caucasians or African Americans. All the subjects genotyped so far (n =118) bore only homogenous wild genotype (C2293/ C2293) at GSTP1 - C2293T locus. This locus seemed to be a monomorphic in Shanghai population. No significant difference in GSTT1 and GSTM1 polymorphic form frequencies could be confirmed among three groups of subjects. An overrepresentation of GSTP1 AG or GG genotype corresponding a less stable and less effective isozyme protein was detected in patients with benzidine related occupational bladder cancer, compared with that in the normal population though a statistical significance was not yet reached (P=0.09, OR=1.96, 95% CI 0.89-4.32,). Conclusion This study suggests that GSTM1 or GSTT1 homozygous deficiency genotypes and their combination do not have a clear impact on bladder cancer incidence in a Shanghai population. It seems that GSTP1 polymorphism is not associated with non-occupational bladder cancer. GSTP1 AG or GG genotype has a higher frequency in the patients with benzidine related occupational bladder cancer, and further work is needed to confirm if GSTP1 AG or GG genotype plays a role in the development of occupational bladder cancer.
γ- Irradiation Effect: Variation of Photosynthetic Activity of Euglena
2002, 15(3): 261-267.
Objective To study the effects of gamma-ray irradiation on carbon fixation (Specific production rate: SPR), CO2 utilization efficiency (CUE) and electron transfer rate (ETR) in the photosynthetic flagellate Euglena gracilis strain Z in a dose-response dependent manner. Methods Euglena cells were cultured in an inorganic nutrient medium containing ammonium chloride or proteose peptone. Cells were exposed to gamma-ray at 5 doses (0, 100, 250, 350, 500 Gy for water). Five days after irradiation, three photosynthetic activities were measured. SPR, which is a carbon uptake rate per unit carbon mass, was determined by 13C tracer methodology. CUE was evaluated using a relation of carbon isotope fractionation in Calvin cycle. ETR in photosystem II (PS II) was measured by a chlorophyll fluorescence analysis. Results Even at a dose of 500 Gy, 80 % of ETR of the non-irradiated control (0 Gy) was sustained, while SPR and CUE were about half the level in the non-irradiated control at 500 Gy. Furthermore, the dose response of ETR was considerably different from the others. Conclusion Our findings suggest that not only PS II but also the Calvin cycle in the photosynthetic system is affected by gamma ray irradiation.
Study on Chromosome Damage Among Nurses Occupationally Exposed to Antineoplastic Drugs in an Oncology Department
YANG Dong-Ping, XU Shi-jie, WANG JIAN-XIN
2002, 15(3): 268-270.