OBJECTIVETo explore the relationship between the expression of heat shock protein 90, 60 and 27 (HSP90, HSP60 and HSP27) and genetic damage in peripheral blood of workers exposed to coke oven emissions.

METHODS288 coke oven workers in a steel factory were divided into the high-dose group and the low-dose group on the basis of environment monitoring result and work place. There were 172 men in high-dose group (workers who worked at the oven top and oven side) and 116 men in low-dose group (workers who worked at the oven bottom and others who were engaged to aided work). 38 workers unexposed occupationally to carcinogenic substances were selected as the control group, who were employed in medical therapy unit nearby 2 kilometers from the steel factory. Their general information, history of personal and occupational exposure, and the work environment were investigated. Blood samples were collected immediately after a shift at the end of a working day from 288 coke oven workers and 38 control workers. Levels of HSP90, HSP60 and HSP27 in peripheral blood lymphocytes were measured by Western blot, and the degree of DNA damage was detected by the comet assay.

RESULTSLevels of HSP90 in peripheral blood lymphocytes in three groups were 0.24 +/- 0.32, 0.12 +/- 0.30 and 0.06 +/- 0.33 respectively. They increased significantly compared with that of the control. But levels of HSP60 and HSP27 were not significantly different among those groups. Compared with the control group, there was significant difference in tail length, olive tail moment et al of SCGE (G +/- s(G)) of occupational exposure workers. High-dose group > low-dose group > control group (P < 0.05). The degree of DNA damage increased with the rise of exposure BaP dose (Spearman r = -0.345, P < 0.01).

CONCLUSIONLevels of HSP90 in peripheral blood lymphocytes and the degree of DNA damage increase with the rise of exposure polycyclic aromatic hydrocarbons (PAHs) dose.

Adult ; Chaperonin 60 ; blood ; Coke ; adverse effects ; Comet Assay ; DNA Damage ; drug effects ; HSP27 Heat-Shock Proteins ; blood ; HSP90 Heat-Shock Proteins ; blood ; Humans ; Lymphocytes ; metabolism ; Male ; Occupational Exposure ; adverse effects ; Polycyclic Aromatic Hydrocarbons ; adverse effects

OBJECTIVETo investigate the effects of polybrominated diphenyl ether-153 (BDE-153) exposure during lactation period on the calcium ion (Ca(2+)) concentration and calcium-activated enzyme levels in cerebral cortical cells among adult rats and to provide a scientific basis for the study on the developmental neurotoxicity of BDE-153.

METHODSForty newborn male rats were randomly and equally divided into four groups according to their body weights and litters: 1, 5, and 10 mg/kg BDE-153 groups and olive oil solvent control group. On postnatal day 10 (PND 10), the BDE-153 groups were administrated BDE-153 (0.1 ml/10 g body weight) by intraperitoneal injection, while the olive oil solvent control group was given an equal volume of olive oil. Two months later, these rats were decapitated, and the cerebral cortex was separated quickly on an ice-cold dish. The Ca(2+) concentration in cerebral cortical cells was measured by flow cytometry. The activities of calcineurin (CaN) and Ca(2+)-Mg(2+)-ATP enzyme were determined by colorimetric method. The mRNA and protein expression of calpain-1 and calpain-2 was measured by real-time quantitative PCR and Western blot.

RESULTSThe mean fluorescence intensities of intracellular Ca(2+) in control group and 1, 5, and 10 mg/kg BDE-153 groups were 10.83, 1.48, 1.93, and 0.62, respectively; the 1, 5, and 10 mg/kg BDE-153 groups had significantly lower intercellular Ca(2+) concentrations than the control group (P < 0.05). The activities of CaN and Ca(2+)-Mg(2+)-ATP enzyme and mRNA and protein expression of calpain-1 showed no significant differences between the 1, 5, and 10 mg/kg BDE-153 groups and control group (P > 0.05). The protein expression of calpain-2 increased as the dose of BDE-153 rose. Compared with the control group (mRNA: 0.81±0.26; protein: 0.15±0.07), the 5 and 10 mg/kg BDE-153 groups had significantly higher mRNA expression of calpain-2 (5 mg/kg BDE-153 group: 1.16±0.52; 10 mg/kg BDE-153 group: 1.32±0.23) and significantly higher protein expression of calpain-2 (5 mg/kg BDE-153 group: 0.31±0.07; 10 mg/kg BDE-153 group: 0.37±0.06) (P < 0.05). The 10 mg/kg BDE-153 group had significantly higher protein expression of calpain-2 than the 1 mg/kg BDE-153 group (0.37±0.06 vs 0.22±0.07, P < 0.05).

CONCLUSIONCa(2+-) mediated calpain-2 activation may be one of the main mechanisms of BDE-153 neurotoxicity.

Animals ; Animals, Newborn ; Ca(2+) Mg(2+)-ATPase ; metabolism ; Calcineurin ; metabolism ; Calcium ; metabolism ; Calpain ; metabolism ; Cerebral Cortex ; metabolism ; Male ; Polybrominated Biphenyls ; toxicity ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the changes of mitochondria membrane potential and cytoplasma cytochrome C as the mechanism of neuron apoptosis induced by B(a)P.

METHODSPrimary neurons were dissociated from cerebral cortex of 1 - 3 days old SD rats and cultured with DMEM incubator at 37 degrees C. After 5 days' cultivation, the neurons were added S9 and B(a)P, and the concentrations of treated B(a)P were 0, 10, 20 and 40 micromol/L respectively. After administering of B(a)P, the neurons were cultivated for 40 hours. Apoptosis rate was measured by flow cytometry using Annexin V-FITC and propidium iodide (PI) staining, and the changes in mitochondrial potential (DeltaPsim) were tested with Rhodamine fluorescence (R2123) technique. Preparation of cytosolic extracts by centrifugation. Western blotting analysis was used to evaluate the level of cytochrome C of cytoplasm.

RESULTSThe apoptotic rate of neuron increased in both the middle dose group and the high dose group compared with controls, and had a dose-response tendency with the concentration of B(a)P. Moreover mitochondrial potential decreased in a dose dependent manner. There was a negative correlation between DeltaPsim and the apoptotic rate of neurons (r = -0.763, P < 0.05); Western blotting analysis showed cytoplasmic cytochrome C level increased significantly, which was positively related with neuron apoptosis (r = 0.831, P < 0.01).

CONCLUSIONLoss of mitochondria membrane potential and increase of cytoplasma cytochrome C may be the main cause of neuron apoptosis induced by B(a)P.

Animals ; Apoptosis ; drug effects ; Benzo(a)pyrene ; toxicity ; Cells, Cultured ; Cytochromes c ; metabolism ; Membrane Potential, Mitochondrial ; Mitochondria ; drug effects ; metabolism ; Neurons ; cytology ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the impact of sub-chronic Aluminium-maltolate [Al(mal)3] exposure on the catabolism of amyloid precursor protein (APP) in rats.

METHODSForty adult male Sprague-Dawley (SD) rats were randomly divided into five groups: the control group, the maltolate group (7.56 mg/kg BW), and the Al(mal)3 groups (0.27, 0.54, and 1.08 mg/kg BW, respectively). Control rats were administered with 0.9% normal saline through intraperitoneal (i.p.) injection. Maltolate and Al(mal)3 were administered to the rats also through i.p. injections. Administration was conducted daily for two months. Rat neural behavior was examined using open field tests (OFT). And the protein expressions and their mRNAs transcription related with APP catabolism were studied using enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR).

RESULTSThe expressions of APP, β-site APP cleaving enzyme 1 (BACE1) and presenilin-1 (PS1) proteins and their mRNAs transcription increased gradually with the increase of Al(mal)3 doses (P<0.05). The enzyme activity of BACE1 in the 0.54 and 1.08 mg/kg Al(mal)3 groups increased significantly (P<0.05). The expression of β-amyloid protein (Aβ) 1-40 gradually decreased while the protein expression of Aβ1-42 increased gradually with the increase of Al(mal)3 doses (P<0.05).

CONCLUSIONResult from our study suggested that one of the possible mechanisms that Al(mal)3 can cause neurotoxicity is that Al(mal)3 can increase the generation of Aβ1-42 by facilitating the expressions of APP, β-, and γ-secretase.

Amyloidogenic Proteins ; genetics ; metabolism ; Animals ; Drug Administration Schedule ; Environmental Pollutants ; administration & dosage ; toxicity ; Gene Expression Regulation ; drug effects ; Male ; Organometallic Compounds ; administration & dosage ; toxicity ; Pyrones ; administration & dosage ; toxicity ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Previous studies demonstrated that interleukin-12 (IL-12) enhances the non-MHC-restricted cytotoxic activity of NK cells and facilitate specific allogeneic human cytotoxic T lymphocyte responses against fresh leukemia cells and cell lines. The Wilms' tumor gene, WT1 mRNA, has been used as a marker of minimal residual disease (MRD) for evaluating therapeutic efficacy of patients with leukemia or myelodysplastic syndrome (MDS). This study was aimed to investigate whether in vitro IL-12 can lower WT1 gene expression in peripheral blood monuclear cells (PBMNC) from patients with leukemia or MDS. PBMNC from these 30 patients and 5 healthy volunteers were cultured at 5 x 10(5) cells/ml alone with or without 100 units/ml of IL-12 for 3 days. WT1 mRNA was measured by competitive reverse transcription polymerase chain reaction (RT-PCR) since WT1 mRNA is considered as a marker of minimal residual disease (MRD) in leukemia and MDS. The results demonstrated that WT1 mRNA in PBMNC of 5 healthy volunteers was less than 10(3) copies/microg of total RNA. Following the 3-day IL-12 treatment, mean WT1 mRNA of PBMNC was reduced from 10(4.8) to 10(4.2) copies/microg of total RNA in 6 CML patients, from 10(5.4) to 10(4.8) copies/microg in 12 MDS patients and from 10(5.0) to 10(4.2) copies/microg in 5 AML patients in CR, but not reduced in 5 of 7 AML in non-CR. It is concluded that IL-12 significantly decrease the quantity of leukemia cells in PBMNC of most patients with MDS, CML and AML in CR. IL-12 may be of considerable benefit in the elimination of MRD in patients with hematological malignancies.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Interleukin-12 ; pharmacology ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Leukocytes, Mononuclear ; metabolism ; Male ; Middle Aged ; Myelodysplastic Syndromes ; genetics ; metabolism ; Neoplasm, Residual ; genetics ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; WT1 Proteins ; biosynthesis ; genetics

OBJECTIVETo observe the analgesic effect of sinomenine on the neuropathic pain rat model induced by SSNI, and discuss its impact on monoamine neurotransmitters in striatal extracellular fluid.

METHODMale SD rats were randomly divided into the sham operation group, the SSNI model group, the gabapentin group (100 mg x kg(-1)), the sinomenine high dose group (40 mg x kg(-1)) and the sinomenine low dose group (20 mg x kg(-1)). Mechanical hyperalgesia and cold pain sensitivity were evaluated by Von Frey hairs and cold spray. Striatum was sampled by microdialysis. High performance liquid chromatography-electrochemical detector (HPLC-ECD) were used to detect the content of such neurotransmitters as monoamine neurotransmitters noradrenaline (NE), dopamine (DA), 5-hydroxy tryptamine (5-HT) and their metabolites dihydroxyphenylacetic phenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA).

RESULTSSNI model rats showed significant improvement in mechanical withdrawal threshold and cold pain sensitivity, significant decrease in intracerebral NE and notable increase in DA, 5-HT and their metabolites. Compared with the model group, the sinomenine high dose group showed significant increase in mechanical withdrawal threshold at 60, 90, 180 and 240 min after abdominal administration (P < 0.01), significant decrease in cold pain sensitivity score during 30-240 min (P < 0.05). Sinomenine can significantly up-regulated NE content in striatal extracellular fluid during 45-135 min (P < 0.05), remarkably reduce DA content and DOPAC at 45, 75 and 135 min (P < 0.05), 5-HT content during 45-135 min, DOPAC during 75-165 min (P < 0.05), and 5-HIAA during 45-135 min (P < 0.05).

CONCLUSIONSinomenine has the intervention effect on neuropathic pain in SSNI model rats. Its mechanism may be related to disorder of monoamine neurotransmitters in striatal extracellular fluid.

Analgesics ; pharmacology ; Animals ; Biogenic Monoamines ; metabolism ; Disease Models, Animal ; Extracellular Fluid ; drug effects ; Male ; Morphinans ; pharmacology ; Neostriatum ; pathology ; Neurotransmitter Agents ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; drug effects ; injuries ; metabolism ; pathology

OBJECTIVEAIM To establish a drug screening model based on transcriptional regulation of estrogen responsive element (ERE) and use it to screen compounds for discovering new ligands of estrogen receptor (ER) subtypes.

METHODA recombinant reporter vector pERE-TAL-SEAP was constructed by inserting a synthetic sequence composed of five tandem copies of EREs upstream of promoter of the reporter vector pTAL-SEAP. The pERE-TAL-SEAP and the internal control plasmid pCMV were transiently co-transfected into Hela cells expressing ER subtype or ER subtype, and the effects of pure ER agonists 17estradiol, phytoestrogen genistein and pure ER antagonist ICI182, 780 on reporter gene SEAP expression were observed.

RESULTIn the Hela cells expressing ER alpha or ER beta subtype, the expression of SEAP gene were induced in a dose dependent manner by 17-estrodiol with a maximal effect at approximately 10 nmol.L-1 and with EC50 of (80.58 +/- 8.51) pmol.L-1 and (103.90 +/- 5.29) pmol.L-1, respectively, so done by phytoestrogen genistein with a maximal effect at 1 mumol.L-1 and with EC50 of (10.86 +/- 0.75) nmol.L-1 and (39.38 +/- 2.26) nmol.L-1, respectively. The maximal level induced by estrodiol and genistein were about 7-14 fold higher than that of vehicle. The pure antiestrogen ICI182, 780 at concentration of 1 mumol.L-1 completely blocked the inductions of 17-estrodiol and genistein.

CONCLUSIONThe cellular drug screening model can be established by transfecting reporter vector pERE-TAL-SEAP in Hela cell lines expressing ER alpha or ER beta. The cell lines can be used to screen compounds with estrogenicity by testing SEAP activity in the culture media of cells growing in microtitier wells. The system should provide an efficient model for screening and analyzing the activity of large numbers of ligands of ER.

Drug Evaluation, Preclinical ; methods ; Estradiol ; pharmacology ; Estrogen Receptor alpha ; Estrogen Receptor beta ; Gene Expression Regulation ; drug effects ; Genes, Reporter ; Genistein ; pharmacology ; HeLa Cells ; Humans ; Ligands ; Promoter Regions, Genetic ; Receptors, Estrogen ; genetics ; Transfection

OBJECTIVETo compare the results of procedure for prolapse and hemorrhoids (PPH) and open hemorrhoidectomy.

METHODSA standard questionnaire was given to all patients after PPH or open hemorrhoidectomy from March 2001 to March 2004. In combination with proctological examination, the results including symptoms relief and recurrence were compared between the two groups.

RESULTSThere were 184 effective questionnaires, including 96 cases in PPH group and 88 in open hemorrhoidectomy group. PPH and open hemorrhoidectomy both relieved prolapse (92.7% vs 96.8%, P=0.282), bleeding (91% vs 81%, P=0.241) and pain (91.7% vs 91.5%, P=0.977). There were no statistical differences in the overall complication rate (30.2% and 29.5%, P=0.923) and recurrence rate (21.8% vs 20.5%, P=0.814) between the two groups. The overall satisfactory degree was 87.5% in PPH group and 84.8% in open hemorrhoidectomy group (P=0.218).

CONCLUSIONPPH is a safe and effective option for prolapsed hemorrhoids compared with open hemorrhoidectomy.

Adult ; Aged ; Digestive System Surgical Procedures ; methods ; Female ; Hemorrhoids ; surgery ; Humans ; Male ; Middle Aged ; Surveys and Questionnaires ; Treatment Outcome

OBJECTIVETo explore the effect of polycyclic aromatic hydrocarbons on the neurobehavioral function of coke oven workers.

METHODS200 healthy adult male coke oven workers were selected from a coke plant of a state-owned steel enterprise in Taiyuan City. 88 controls occupationally unexposed to polycyclic aromatic hydrocarbons (PAHs) were selected from the same enterprise. All the subjects participated in this investigation voluntarily in their consent. Concentration of B(a)P in the working environment was monitored by High Performance Liquid Chromatography (HPLC). Urine samples were sampled immediately after working shifts. The level of urinary 1-hydroxypyrene was determined by HPLC. General information of workers correlated with the investigation was collected in a questionnaire according to the same criteria by well-trained investigators. Neurobehavioral core test battery (NCTB) recommended WHO was performed on coke oven workers and controls to test the neurobehavioral changes and the mood state.

RESULTSthe concentration of B(a)P at oven bottom,oven side and oven top were 0.0195 microg/m3, 0.186 microg/m3 and 1.624 microg/m3 respectively, that at oven side and oven top being higher than the one stipulated by the occupational hygiene criterion. Urinary 1-hydroxypyrene was significantly different between the exposure group (3.42 +/- 0.98 micromol/mol creatinine) and control group (2.75 +/- 1.09 micromol/mol creatinine). No significant differences were found between exposure group and control group of age, working years, smoking, drinking and unhealthy food consumption; however, compared to the controls, the scores of total digital span, the forward digital span, and right dotting in the coke oven workers were lower, but that of total dotting was higher, with a statistical significance. According to urinary 1-hydroxypyrene concentration, all the subjects were divided into three groups. (<3.10 micromol/mol creatinine, 3.10 micromol/mol creatinine, >3.87 micromol/mol creatinine). Significant differences of the total digital span, the forward digital span, backward digital span, digit symbol and Benton visual retentions existed in different urinary 1-hydroxypyrene concentration groups and showed a dose-response tendency. Results of multiple stepwise regression analysis and correlation analysis showed that the level of urinary 1-hydroxypyrene affected memory and perception of coke oven workers and negative correlations between the level of urinary 1-hydroxypyrene and changes in neurobehavioral function were found.

CONCLUSIONPAHs mainly causes decrease of memory and perception in coke oven workers.

Adult ; Air Pollutants, Occupational ; analysis ; Coke ; Humans ; Male ; Memory ; Neuropsychological Tests ; Occupational Exposure ; Polycyclic Aromatic Hydrocarbons ; urine

OBJECTIVETo investigate the brain oxidative stress injury induced by nano-alumina particles in ICR mice.

METHODSSixty male ICR mice were randomly divided into 6 groups: control group, solvent control group, 100 mg/kg micro-alumina particles group, 3 groups exposed to nano-alumina particles at the doses of 50, 100 and 200 mg/kg. The mice were exposed by nasal drip for 30 days. Then levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) in brain tissues of mice were detected.

RESULTSThere was no difference of SOD activity in mouse brain between control group [(17.32 +/- 6.23)U/gHb] and 50 mg/kg nano-alumina particles group [(17.89 +/- 1.82) U/gHb]. The SOD activity [(4.93 +/- 2.30)U/gHb] in 200 mg/kg nano-alumina particles group was significantly lower than that in control group (P < 0.05). The MDA levels in 3 nano-alumina particles groups were (0.76 +/- 0.13), (1.00 +/- 0.30) and (1.16 +/- 0.39)nmol/ml, respectively, which were significantly higher than that [( 0.24 +/- 0.09)nmol/ml] in control group (P < 0.05). The GSH levels in 3 nano-alumina particles groups were (0.72 +/- 0.08), (0.55 +/- 0.19) and (0.61 +/- 0.20)mg/gpro, respectively, which were significantly lower than that [(1.55 +/- 0.34)mg/gpro]] in control group (P < 0.05). The CAT activity in 50 and 100 mg/kg nano-alumina particles groups were (10.40 +/- 3.84) and (10.40 +/- 2.00)U/mgpro, respectively, which were significantly higher than that [(5.79 +/- 0.96) U/mgpro] in control group (P < 0.05). The CAT activity [(3.25 +/- 1.04)U/mgpro] in 200 mg/kg nano-alumina particles group was significantly lower than that in control group (P < 0.05 ).

CONCLUSIONNano-alumina particles can induce the oxidative stress damage in brain tissues of mice.

Aluminum Oxide ; toxicity ; Animals ; Cerebral Cortex ; metabolism ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred ICR ; Nanoparticles ; toxicity ; Oxidative Stress ; Superoxide Dismutase ; metabolism