AIMTo synthesize novel derivatives of hydroxylbenzenedisulfonanilide with high insecticidal activity against the Fasciola hepatica.

METHODSo-(m-, p-) Chlorphenol were used to synthesize the title compounds by sulphonation and nucleiphilic-substitution reaction. The uncoupling activity (insecticidal activity) of these compounds were tested by determining the influence on mitochondrial respiration control ratio (RCR) and the variation of inorganic phosphate in oxidative phosphorylation (delta Pi).

RESULTSCompounds 1-14 are new compounds. The structures of the compounds were determined by IR, HNMR and elemental analysis. Most new compounds have relatively high uncoupling activities, especially compounds 3, 5, 6 and 9.

CONCLUSIONCompounds 3, 5, 6 and 9 will become novel fasciolicides and are worth further studying.

Anilides ; chemical synthesis ; chemistry ; pharmacology ; Animals ; Anthelmintics ; chemical synthesis ; chemistry ; pharmacology ; Fasciola hepatica ; drug effects ; Mitochondria, Liver ; physiology ; Molecular Structure ; Oxygen Consumption ; drug effects ; Sulfonamides ; chemical synthesis ; chemistry ; pharmacology

Objective To establish a QAMS method for content determination of six compositions (chlorogenic acid, caffeic acid, cryptochlorogenin acid, isochlorogenic acid A, isochlorogenic acid C and loganin) from Lonicerae Japonicae Caulis; To verify the feasibility and applicability of this method in quality control of Lonicerae Japonicae Caulis. Methods Chlorogenic acid was set as internal reference substance. The HPLC analysis was performed on a Waters Symmetry C18 column (4.6 mm × 250 mm, 5 μm) with a mobile phase consisted of acetonitrile and 0.4% phosphoric acid solution in gradient elution manner at a flow rate of 1 mL/min. The column temperature was maintained at 35 ℃, and the detection wavelength was set at 327 nm for chlorogenic acid, caffeic acid, cryptochlorogenin acid, isochlorogenic acid A, isochlorogenic acid C and 236 nm for loganin. Results The relative correction factors of caffeic acid, cryptochlorogenin acid, isochlorogenic acid A, isochlorogenic acid C and loganin were established; there was no obvious difference between calculated value of QAMS and measured value of external standard method. Conclusion The quality control mode of QAMS can be used for multi-index synchronization quality evaluation of the six compositions from Lonicerae Japonicae Caulis.

OBJECTIVETo investigate HLA-DRB1 gene polymorphism in patients with Keshan disease (KD) in the north of China, and its relation to KD in the core families.

METHODSPolymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method was used to determine HLA-DRB1 genotypes in 118 KD patients, including 63 with latent KD and 55 with chronic KD. Sixty-five normal from the same area were selected as controls. The haplotype based haplotype relative risk (HHRR) and transmission disequilibrium test (TDT) methods were used to analyze the genetic association and linkage of HLA-DRB1 with KD in 18 KD core families.

RESULTS(1) Thirteen kinds of alleles of HLA-DRB1 gene were found in all patients and the controls. (2) The distributive frequency of DR7 allele was significantly lower in chronic KD patients than that in controls (P< 0.01, OR is 0.1695). (3) The distributive frequency of DR7 allele was statistically lower in chronic KD (P< 0.01, OR is 0.091) and showed no differences in latent KD patients as compared with the controls. (4) DR15 allele of HLA-DRB1 gene showed significant association (chi square is 9.32, P< 0.01) and linkage (chi square is 7.40, P< 0.01) with KD patients in the core families.

CONCLUSIONThe results show that there might be the genetic susceptibility in the pathogenesis of KD. DR7 allele of HLA-DRB1 gene might be the protective gene of KD. Patients with DR7 allele might be more difficult to become to chronic KD. DR15 allele of HLA-DRB1 gene might be linked to the susceptive site of KD.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Cardiomyopathies ; genetics ; Child ; Family Health ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Haplotypes ; Humans ; Linkage Disequilibrium ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Young Adult

OBJECTIVETo investigate cytotoxicity and genotoxicity of benzo(a)pyrene (B(a)P) by 16HBE-CYP1A1 cells which are human bronchial epithelial cell with CYP1A1 transformed.

METHODSExpression of CYP1A1 and mEH of cell models were tested by real-time quantitative polymerase chain reaction. Cells were treated with 0, 1, 5, 10 and 20 micromol/L B(a)P for 24 h. Adverse effects of B(a)P were tested by cytokinesis-block micronucleus (CBMN) cytome assays. Cytotoxicity was assessed by the nuclear division index (NDI), frequency of necrotic and apoptotic cells. Genetic damages were assessed by frequencies of CBMN, nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs).

RESULTSHigh levels of CYP1A1 and mEH were found in 16HBE-CYP1A1 cells (relative mRNA content was 7.8 x 10(-4) and 0.030 respectively). In 16HBE-CYP1A1 cells, NDI were decreased in 1, 5, 10 and 20 micromol/L B(a)P treated groups, 1.92 +/- 0.04, 1.71 +/- 0.01, 1.61 +/- 0.04, and 1.41 +/- 0.01, respectively; and lower than control group (2.08 +/- 0.03). Compared with control group ((82.67 +/- 6.66)%), the binucleated cells ratios were decreased, (76.33 +/- 3.51)%, (66.33 +/- 0.58)%, (51.67 +/- 1.53)% and (39.0 +/- 1.0)% respectively.Necrotic cells ratios were (1.93 +/- 0.42)%, (2.20 +/- 0.53)%, (8.07 +/- 0.90)% and (15.27 +/- 2.80)%, respectively, higher than control group ((0.47 +/- 0.11)%). The differences were significant (F values were 899.94, 303.33, 240.87, P < 0.01). Apoptotic cells were increased at lower groups and decreased to normal at higher groups treated by B(a)P. They were (1.20 +/- 0.53)%, (2.00 +/- 0.20)%, (1.47 +/- 0.12)%, (1.20 +/- 0.00)% and (1.20 +/- 0.00)%, respectively. Analysis on biomarkers of genetic damage, the significant dose-effect relationship were observed in NPBs and NBUDs (F values were 50.23, 121.09, P < 0.01, respectively). Frequencies of NPBs were (4.67 +/- 2.89) per thousand, (7.33 +/- 1.53) per thousand, (10.67 +/- 2.08) per thousand and (11.00 +/- 1.00) per thousand respectively. Frequencies of NBUDs were (2.33 +/- 0.58) per thousand, (4.00 +/- 1.00) per thousand, (5.00 +/- 1.00) per thousand, and (7.67 +/- 1.16) per thousand respectively. However, the dose-relationship of CBMN last only to 10 micromol/L B(a)P treated groups in 16HBE-CYP1A1 cells, and frequencies of CBMN were (8.33 +/- 3.21) per thousand, (14.67 +/- 1.15) per thousand, respectively. Frequency of CBMN was (16.67 +/- 2.88) per thousand in 20 micromol/L B(a)P treated group, lower than 10 micromol/L B(a)P treated group ((17.67 +/- 2.08) per thousand). In 16HBEV control cells, the cytotoxicity was found only in higher B(a)P treated groups and frequencies of CBMN, NPBs and NBUDs were increased also. While no significant differences were observed between 5, 10, 20 micromol/L B(a)P treated groups (they were (6.37 +/- 2.08) per thousand, (9.33 +/- 1.52) per thousand, (9.33 +/- 3.21) per thousand; (4.33 +/- 1.53) per thousand, (6.00 +/- 2.65) per thousand, (5.33 +/- 1.53) per thousand and (2.33 +/- 0.58) per thousand, (3.33 +/- 1.16) per thousand, (3.67 +/- 1.16) per thousand, respectively).

CONCLUSIONSThe genetic damages were more severe after treated with activated B(a)P, which may be induced by decreased NDI, increased necrotic cells and inhibition of apoptosis.

Apoptosis ; drug effects ; Benzo(a)pyrene ; toxicity ; Cell Division ; drug effects ; Cell Line, Transformed ; DNA Damage ; Humans ; Micronuclei, Chromosome-Defective

OBJECTIVETo explore the effect of glutathione (GSH) and sodium selenite on the metabolism of arsenic in the liver, kidney and blood of mice exposed to iAsIII through drinking water.

METHODSThe mice were randomly divided into control, arsenic, GSH and sodium selenite group, respectively. And each group had eight mice and the mice were exposed to 50 mg/L arsenite by drinking water for 4 weeks. Mice were intraperitoneally injected with GSH (600 mg/kg) and sodium selenite (1 mg/kg) for seven days from the beginning of the fourth week. At the end of the fourth week, liver, kidney and blood were sampled to assess the concentrations of inorganic arsenic (iAs), monomethylarsenic acid (MMA), dimethylarsenic acid (DMA) by hydride generation trapping by ultra-hypothermia coupled with atomic absorption spectrometry.

RESULTSThe liver DMA (233.76 +/- 60.63 ng/g) concentration in GSH group was significantly higher than the arsenic group (218.36 +/- 42.71 ng/g). The concentration of DMA (88.52 +/- 30.86 ng/g) and total arsenic (TAs) (162.32 +/- 49.45 ng/g) in blood of GSH group was significantly higher than those [(45.32 +/- 12.19 ng/g), (108.51 +/- 18.00 ng/g), respectively] of arsenic groups(q values were 3.06, 6.40, 10.72 respectively, P < 0.05). The primary methylated index (PMI) (0.65 +/- 0.050) and secondary methylated index (SMI) (0.55 +/- 0.050) in liver sample of GSH group were significantly higher than those (0.58 +/- 0.056, 0.44 +/- 0. 093) in arsenic group. In blood samples, the PMI (0.85 +/- 0.066) in GSH group was significantly higher than that (0.54 +/- 0.113) in arsenic group (q values were 3.75, 5.26, 4.21 respectively, P < 0.05). However, no significant difference was identified between sodium selenite and arsenic groups in liver, kidney or blood samples. And no significant difference was detected in kidney samples among all arsenic exposing groups.

CONCLUSIONExogenous GSH could promote the methylated metabolism of iAsIII, but sodium selenite showed no significant effects.

Animals ; Arsenic ; analysis ; metabolism ; Arsenic Poisoning ; metabolism ; Environmental Exposure ; Female ; Glutathione ; pharmacology ; Male ; Mice ; Mice, Inbred Strains ; Sodium Selenite ; pharmacology ; Water Supply

Objective To describe the prevalence and risk factors for suicide ideation among college students in Chongqing city. Methods Data on suicide ideation and related factors were collected from 9808 college students at 11 colleges randomly selected in Chongqing. A multiple logistic regression model was used to identify risk factors for suicide ideation. Results 1279 (13.0%) of the 9808 students reported suicide ideation and the constituent ratio of boys and girls was 3:4 whileriskfactors for suicide ideation were ranked as follows: high frequency of feeling hopeless in prior year (OR=5.07,95%CI: 4.27-6.02); having psychological problems in recent 1 month that affecting daily lives and learning(2.07,1.79-2.38); relatives having suicide behavior (1.77,1.52-2.08); having had sexual experience (1.95,1.65-2.30); being female (1.66,1.45-1.90) and friends who had had suicide attempts(1.46,1.28-1.67);having diseases in the last 1 month that affecting daily lives and learning (1.29,1.08-1.52). Conclusion The prevalence of suicide ideation among these college students was high that calls the development,implementation and assessment of suicide prevention plans for college students that focusing on the risk factors identified for suicide ideation.

OBJECTIVETo investigate the relationship between lymphocyte DNA damage and polycyclic aromatic hydrocarbons (PAHs) exposure in coke oven workers.

METHODSTwo hundred and thirty-five coke oven workers and 30 controls were selected in this study. Alkaline single-cell gel electrophoresis was used to evaluate the lymphocyte DNA damage, HPLC was employed to measure 1-hydroxypyrene levels in spot urine samples which were obtained at the end of a workweek (4 days of 8 hours/day) and personal information including occupational exposure, age, sex, smoking and drinking status was collected by the questionnaire.

RESULTSThe lymphocyte DNA damage level expressed as olive moment in coke oven workers was significantly higher than that of controls [2.47 (0.22 approximately 46.68) vs 0.94 (0.42 approximately 4.21), P < 0.01], and correlation between urinary 1-hydroxypyrene concentrations and olive moment was found (Spearman Partial correlation coefficient = 0.22, P < 0.01) in coke oven workers. The 1.9 of olive moment value was used as the limit to determine whether the subject DNA damage was positive. The coke oven workers had significantly higher risk in DNA damage (adjusted OR = 5.38, 95% CI = 2.07 approximately 14.08) than did controls, and dose-response relationships were also found between external exposure (exposure category) or internal doses (urinary 1-hydroxypyrene) and DNA damage.

CONCLUSIONThere are dose-effect and dose-response relationships between PAHs exposure and lymphocyte DNA damage in coke oven workers.

Adult ; Animals ; Coke ; adverse effects ; DNA Damage ; drug effects ; Dose-Response Relationship, Drug ; Female ; Humans ; Lymphocytes ; metabolism ; Male ; Occupational Exposure ; Polycyclic Aromatic Hydrocarbons ; poisoning ; Pyrenes ; analysis ; metabolism ; Surveys and Questionnaires

OBJECTIVETo investigate DNA and chromosome damage in peripheral blood lymphocyte of coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs).

METHODSOne hundred and thirty-seven coke oven workers and 50 controls without occupational PAHs exposure were investigated. Comet assay and cytokinesis-block micronucleus (CBMN) detection were used to evaluate DNA and chromosomal damage levels in peripheral blood lymphocyte. Urinary 1-hydroxypyrene level was used to assess the personal internal PAHs exposure dose. Personal information including occupational history, age, sex, smoking and drinking status was collected by questionnaire.

RESULTSUrinary 1-hydroxypyrene level in coke oven workers [(5.76 +/- 1.04) micro mol/mol Cr] was significantly higher than that in controls [(0.70 +/- 0.32) micro mol/mol Cr]. The rate of CBMN and comet tail moment of lymphocyte in coke oven workers [8.0 per thousand (0.0 per thousand - 30.0 per thousand ) and 2.09 (0.31 - 75.41), respectively] were higher than those in controls [3.5 per thousand (0.0 per thousand - 13.0 per thousand ) and 1.05 (0.11 - 6.63), P < 0.05]. In controls, the comet moment in smokers was significantly higher than that in non-smokers [1.44 (0.23 - 6.63) vs 0.81 (0.11 - 3.47), P < 0.05]. According to the length of work, 137 coke oven workers were classified into 3 groups i.e. 0.5 yrs , 16.0 yrs and 22.0 yrs group, and the comet moments were 1.34 (0.31 - 37.84), 2.32 (0.49 - 52.97) and 3.20 (0.45 - 75.41) respectively after adjusting the age, sex, smoking, drinking and level of urinary 1-hydroxy-pyrene. There was a rising tendency along with the increase in length of work.

CONCLUSIONUnder present PAHs exposure levels, both comet assay and Cytokinesis-block micronucleus test could detect PAHs-induced genotoxicity in coke oven workers, and comet assay is more suitable to assess the cumulative damage effect on DNA.

Adult ; Coke ; Comet Assay ; DNA Damage ; Female ; Humans ; Lymphocytes ; metabolism ; Male ; Middle Aged ; Occupational Exposure ; analysis ; Polycyclic Aromatic Hydrocarbons ; poisoning ; Pyrenes ; analysis ; Time Factors

OBJECTIVETo investigate the association between polymorphisms of metabolic enzyme genes and chromosomal damage risk in peripheral blood lymphocytes among coke oven workers.

METHODSOne hundred and fourty-nine coke oven workers and 24 referents without occupational polycyclic aromatic hydrocarbons (PAH) exposure were recruited in this study. Urinary 1-hydroxypyrene levels were measured as the internal dose of PAH exposure. The 6 per 1 000 of micronucleus value was used as the cut-off value to determine whether the individual's chromosomal damage was positive. The genotypes of CYP1A1, GSTM1, GSTT1, GSTP1, CYP2E1, NQO1, NAT2 and mEH genes were determined by PCR-based methods. Multiple logistic regression was used to calculate the adjusted ORs and the 95% CI for the risk of chromosomal damage and to analyze the gene-gene interaction.

RESULTSIn 173 subjects, after adjusting the occupational exposure, age, sex, smoking and drinking status, the subjects with GSTM1 null genotype have significantly higher risk for chromosomal damage than subjects with GSTM1 positive genotype (adjusted OR = 2.01, 95% CI = 1.03 -3.91). Compared with the wild homozygotes at P187S site of NQO1 gene, the variant homozygotes have significantly higher risk for chromosomal damage (adjusted OR = 3.18, 95% CI = 1.18 - 8.62). The subjects with variant allele at H113Y site of mEH gene have significantly lower risk for chromosomal damage (adjusted OR = 0.40, 95% CI = 0.19 - 0.88). No significant associations were found for other gene polymorphisms and chromosomal damage risk. In addition, the gene-gene interactions were also found among GSTM1, NQO1 gene P187S and mEH gene H113Y polymorphisms for the risk of chromosomal damage risk.

CONCLUSIONSignificant associations between genetic polymorphisms in GSTM1, NQO1 and mEH gene and risk for chromosomal damage were found among occupational PAH-exposed workers, which related to the mechanism of PAH carcinogenesis.

Adult ; DNA Damage ; genetics ; Epoxide Hydrolases ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Glutathione Transferase ; genetics ; Humans ; Logistic Models ; Lymphocytes ; metabolism ; Male ; Middle Aged ; Multivariate Analysis ; NAD(P)H Dehydrogenase (Quinone) ; genetics ; Occupational Exposure ; Polycyclic Aromatic Hydrocarbons ; poisoning ; Polymorphism, Genetic ; Pyrenes ; analysis ; Risk Factors

OBJECTIVETo investigate the relationship between the urinary 1-hydroxypyrene level and cytokinesis-block micronucleus and the olive moment of comet assay in peripheral blood lymphocyte in coke oven workers.

METHODSOne hundred and thirty-three workers from a coke plant and 28 referents without occupational PAH exposure were recruited in this study. Urinary level of 1-hydroxypyrene was measured by alkaline hydrolysis combined with high performance liquid chromatography as an internal exposure dose, and the DNA and chromosomal damage of peripheral blood lymphocyte were evaluated with comet assay and cytokinesis-block micronucleus method. Personal information including occupational history, age, sex, smoking and alcohol drinking, was collected by questionnaire.

RESULTSThere existed a good correlationship between the urinary level of 1-hydroxypyrene and frequency of micronuclei per 1 000 binucleated cells or the olive moment of comet assay in the study subjects, after adjusting for sex, age, smoking and alcohol drinking (r > 0.25, P < 0.01). One hundred and sixty-one subjects were divided into three groups by their urine 1-hydroxypyrene level (expressed as 0.30 - 2.44, 2.45 - 7.09 and 7.10 - 33.10 micro mol/mol Cr), and the geometric means of their urinary levels of 1-hydroxypyrene were 1.14, 4.32 and 12.49 micro mol/mol Cr, respectively. After adjusting for age, sex, smoking and alcohol drinking by multiple nonparametric analysis of covariance, the median of olive moment of comet assay in the group of 7.10 - 33.10 micro mol/mol Cr was 3.67, significantly higher than that in the groups of 0.30 - 2.44 and 2.45 - 7.09; and the micronuclei frequencies in the groups of 2.45 - 7.09 and 7.10 - 33.10 micro mol/mol Cr were 8.00 per thousand and 7.50 per thousand, respectively, significantly higher than that in the group of 0.30 - 2.44 micro mol/mol Cr (6.00 per thousand ).

CONCLUSIONSThe comet assay of peripheral blood lymphocyte was more suitable to detect the PAHs-induced early genotoxicity, than the cytokinesis-block micronucleus.

Adult ; Coke ; adverse effects ; Comet Assay ; Female ; Humans ; Male ; Micronuclei, Chromosome-Defective ; drug effects ; Micronucleus Tests ; Occupational Exposure ; adverse effects ; Pyrenes ; metabolism