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OBJECTIVE： To study the effects of cimetidine on low dose rate irradiation-induced liver cell apoptosis in Beagle dogs. METHODS： Healthy male Beagle dogs were randomly divided into normal control group， model control group， positive drug group （lentinan， 21.33 mg/kg） and cimetidine low-dose， medium-dose and high-dose groups （5.33， 10.67， 21.33 mg/kg）， with 4 Beagle dogs each. Except for normal control group， other groups were given 60Co-γ accumulative irradiation （dosage rate： 0.040 8 mGy/min） for 23 d； the medication groups were given relevant medicine orally before irradiation， once a day. Twenty-four hours after stopping irradiation， TUNEL method was used to detect the apoptosis of liver cells in Beagle dogs. The percentage of apoptotic cells was calculated. The expression level of apoptosis-related proteins （Bax， Bcl-2， Caspase-3， p53） in liver tissue was detected by immunohistochemistry. RESULTS： Compared with normal control group， apoptotic cells and Bax， Caspase-3， p53 positive cells were increased significantly in liver tissue of Beagle dogs in model control group； the percentage of apoptotic cells， protein expression levels of Bax， Caspase-3 and p53 were increased significantly； Bcl-2 positive cells were decreased significantly， and its protein expression level was decreased significantly （P＜0.05 or P＜0.01）. Compared with model control group， above positive cells of liver tissue in Beagle dogs were changed to different extents in medication groups； the percentage of apoptotic cells and protein expression levels of p53 in medication groups， protein expression levels of Bax in positive drug group， cimetidine low-dose and high-dose groups as well as protein expression levels of Caspase-3 in cimetidine groups were decreased significantly； protein expression levels of Bcl-2 were increased significantly in cimetidine groups. The percentage of apoptotic cells in cimetidine medium-dose and high-dose groups as well as protein expression levels of Caspase-3 in cimetidine groups were all lower than positive control group. Protein expression level of p53 in cimetidine low-dose group was significantly higher than positive drug group （P＜0.05 or P＜0.01）. CONCLUSIONS： Cimetidine can inhibit the low dose rate irradiation-induced apoptosis of liver cells in Beagle dogs， and certainly protect liver cells against irradiation. The mechanism of it may be associated with up-regulating the protein expression of Bcl-2 and down-regulating the protein expression of Bax， Caspase-3 and p53 in liver cells.
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Objective To investigate the radioprotective effect of cimetidine on survival rate and hematopoietic system in acutely irradiated mice.Methods The total body irradiation doses were 6.0Gy and 8.0Gy respectively at 1.01Gy/min rate. Sixty healthy male C57BL/6 mice were randomly divided into control group, model group, positive-drug (523) group and cimetidine groups (33.3mg/kg, 100mg/kg and 300mg/kg). Each group had ten mice. The mice were given intragastric administration of cimetidine for 6d before the irradiation in cimetidine groups, and 523 was administered before irradiation once a day for one day in 523 group, and at 5h after irradiation, was given again. The 30d survival rate after 8.0Gy irradiation was recorded. The peripheral blood cells, bone marrow DNA content and frequency of micronucleated polychromatic erythrocytes (fMNPCE) were determined 30d after 6.0Gy irradiation.Results After 8.0Gy irradiation, all the mice died on 21th day in model control group. The survival rates in cimetidine groups were 50%, 20% and 30%, respectively. After 6.0Gy irradiation on 30th day, compared with control group, the peripheral white blood cells (WBC) and bone marrow DNA content were decreased significantly (P<0.01,P<0.05) in model group, and fMNPCE was increased significantly (P<0.05). Compared with model group, WBC was significantly increased in 300mg/kg cimetidine group (P<0.01). In cimetidine groups, the bone marrow DNA content was increased significantly after irradiation (P<0.01 orP<0.05), and the fMNPCE was decreased significantly (P<0.01 orP<0.05) and tended towards normal.Conclusion Cimetidine could improve 30d survival rate of acutely irradiated mice and has good protective effect on hematopoietic system.
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Objects To study the protective effects of cimetidine against oxidative stress in rats induced by cumulative low-dose irradiation.Methods Sixty SD rats were randomly divided into 6 groups (10 each):normal control group,model control group,lentinan group [89mg/(kg.d)] and 3 dose groups of cimetidine.After oral administration,all the rats were exposed to γ-ray irradiation 8 hours/day for 12 days,and sacrificed on the 13th day.The activities of superoxide dismutase (SOD),glutathione peroxidase (GPx),catalase (CAT) and the content of malondialdehyde (MDA) in serum,liver,thymus and spleen were determined.By using the superoxide anion radical system,hydroxyl radical system,H2O2 radical system,oxidation system of linoleic acid induced by alkane radical system and diphenyl picryl hydrazinyl radical (DPPH) radical system,the antioxidation activities of cimetidine were detected.Results The activities of SOD in liver and thymus decreased significantly,the GPx activity in serum,liver and spleen decreased significantly and MDA level in serum,liver and spleen increased significantly after 0.3Gy cumulative ionizing radiation.Cimetidine enhanced the activities of antioxidant enzymes in serum and organs,and reduced the MDA level.In a certain concentration range,cimetidine had different scavenging effects onto these radical systems,and showed good performance in hydroxyl radical.Conclusion Cimetidine can effectively ameliorate the oxidative stress from low-dose cumulative irradiation by scavenging free radicals,increase the activity of antioxidant enzymes and reduce the content of lipid peroxidation products,thus presents a potential radio protective effect.
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OBJECTIVE: To compare and analyze the risk of formaldehyde hazards in a plywood manufacturing factory using two risk assessment methods,and to evaluate the occupational health risk. METHODS: Occupational health investigation and formaldehyde detection for workplaces were carried out in a plywood manufacturing factory in Shandong province. The risk ratings of different posts were assessed by US Environmental Protection Agency( EPA) inhalation risk( EPA assessment model) and Singapore Semi-quantitative Assessment Model( MOM assessment model). The risk classification results of the 2 risk assessment methods were compared and analyzed. RESULTS: The concentration of airborne formaldehyde on the positions of shaving,woods feeding,gluing,hot milling,hot pressing,sanding and reprocessing were 0. 25,0. 13,1. 47,0. 72,0. 92 and 0. 58 mg/m~3,respectively. By the EPA assessment model,all of the positions were evaluated as high carcinogenic risk. Through the MOM assessment model,the feeding position was evaluated as medium risk,the positions of shaving,hot milling,hot pressing sanding and reprocessing were high risk,and the position of gluing was higher risk. CONCLUSION: It suggests that there is a high formaldehyde exposure in several posts in the plywood production processing. EPA assessment model is a suitable for occupational health risk assessment for formaldehyde exposure.
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OBJECTIVE: To establish the cell model using human leukemia cell line HL-60 for exposure of coke oven emissions( COE) in vitro and to explore the mechanism of COE-induced acute toxicity in HL-60 cells. METHODS: HL-60 cells were collected in their logarithmic growth phase and cultured in medium that had final concentrations of COE in 2. 5,5. 0,10. 0 and 20. 0 mg / L for 24 hours. Cell survival rate was examined by CCK-8 assay. The cytotoxicity was evaluated using lactate dehydrogenase release assay. Reactive oxygen species( ROS) production was determined by the 2',7'-dichlorofluorescein diacetate and nitroblue tetrazolium method. The activation of nuclear factor-κB( NF-κB) pathway was evaluated by western blot. RESULTS: With the increasing exposure concentrations of COE,the cytotoxicity of HL-60 cells increased( P < 0. 01),the cell survival rate decreased( P < 0. 01),intracellular ROS decreased( P < 0. 01),whereas extracellular ROS increased( P < 0. 01). These changes had a dose-effect relationship. The levels of phospho-nuclear factor-kappa B p65 and phospho-inhibitor of kappa Bα were higher in all the COE-treated cells compared with untreated cells( P < 0. 05),with no dose-effect relationship. CONCLUSION: COE could cause acute toxicity in HL-60 cells in a doseeffect relationship. The mechanism may be related to the COE-induced in-balanced ROS release and removal,leading to the activation of NF-κB pathway. HL-60 cells can be used as a common cell line for COE hematotoxicity analysis.
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Objective:To prepare old tea buccal tablets using wet granulation method and optimize the preparation technology. Methods:The amount of each adjuvant was studied by single factor experiments, and the formula of the buccal tablets was optimized by the orthogonal experiments using taste and disintegration time as indices. Results:The optimal formula was composed of old tea ex-tract 30 g,mannitol 60g,PEG6000 20 g,aspartame 10 g,citric acid 10 g and menthol crystal 1 g. All the tested indices including ap-pearance, hardness and disintegration time met the requirements described in Chinese pharmacopeia. Conclusion: The preparation technology is reasonable and feasible for the industrial production.
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Objective To investigate the combined biological effects of low dose radiation,carbon monoxide,benzene and noise on rats.Methods Sixteen male SD rats were randomly divided into experiment group and control group.The experiment group was exposed to carbon monoxide,benzene,low dose radiation and noise daily,the control group was in common environment.Peripheral blood,organ index,and marrow DNA content were detected.Two-dimensional electrophoresis (2-DE) was performed on serum protein analysis.Differential expressed proteins were identified by a matrix assisted laser desorption/ionization time of flight mass spectrometry (MAIDI-TOF-MS).Results Compared to control group,the liver index,spleen index,thymus index,leukocytes,platelets count,and marrow DNA content of the experiment group were decreased significantly (t =2.732,4.141,3.053,2.211,2.668,11.592,P ＜0.05).12 altered proteins were detected and through identification,3 proteins were definite in terms of serum amyloid A-4 protein (SAA4),trichoplein keratin filament-binding protein (TCHP) and tubulin alpha-4A chain (TUBA4A).Conclusions The hematopoietic system and immune system of rats are damaged significantly with the changes of several serum protein expressions by the combined exposure of low dose radiation,carbon monoxide,benzene and noise.This study may provide new information for the mechanism of the combination effects.
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Purpose To construct a recombined antitumor peptide and to analyze its bioactivity. Methods Constructing a recombined gene and inserting the pGEX-4T-3 vector. The recombined protein was expressed in E. coli BL21 and purified with Amylose Resin. Then, citrostatin was subjected to the following tests separately: inhibition of endothelial cell proliferation, MTT test of cytotoxicity and inhibition of endothelial cell tube formation on ECMatrix. Results Citrostatin significantly inhibited the proliferation of human endothelial cell ECV304(IC_(50) = 2.28 μmol/L) .It also significantly inhibited the proliferation of human tumor cell 1990 and NCI-H64O(IC_(50) = 9.24,2.74 μmol/L) ,and the inhibitory effect became more marked with the increase of citrostatin concentration. The inhibitory effects of citrostatin on endothelial cell tube formation was also confirmed . Conclusion An antitumor peptide, citrostatin, has been successfully constructed and purified, which showed anti-angiogenesis effect and direct cytotoxic effect on tumor cells.
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The abdominal CT findings of cirrhosis of advanced schistosomiasis in 262 cases were analyzed.All the cases had the calcification in liver in varying degrees,hypodense structure in junction areas and blood vessel in centre,calcification in portal vein system,calcification of colon and so on.The characteristics of CT performance can provide the evidence for defferential diagnosis.
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Objective To study the profiles of decompression sickness(DCS) in various kinds of animals and to find out the target organ of decompression sickness by providing a basic experimental method for establishing animal models.Method Eleven kinds of animals were exposed to different pressures for different times at different compression/decompression rates.They were monitored at the precordial regions with Doppler flow meter for bubble sounds after decompression to normal pressure,to obtain a record about the developing course of the DCS.Pathological examinations of the bulbar conjunctiva were also made. Result Bubble sound of grade IV were recorded at the precordial regions after decompression.Among them,75%~100% incurred DCS with a diverse extent. Animals developed DCS showed vascular spasm,dysfunction and endothelial tumefaction.Conclusion Each of the 11 kinds of animals can serve as a model of DCS and the processes of development of DCS in various animals are similar.Blood vessels are the target organs of decompression sickness.
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AIM: To observe the effect of small dose ephedrine on hypote ns ion as the lithotomy position in laying down legs after the aged in the operatio ns with epidural anesthesia. METHODS: Twenty-seven ASA Ⅰ-Ⅱma le patients, aged 65-83 (71? 6.5 ) years undergoing transurethral resection of prostate (TURP) with the lithotomy position were randomly assigned to two gro ups by double blind method: ephedrine group (n=13) and contrasti ve group (n=14). The continual epidural anesthesia was administe red in T 12 -L 1 and L 3-4 for all patients used 1.5 % lidocaine. W hen the operation was finished off, before thirty seconds of horizontal position laying down legs, 15 mg ephedrine was iv at ephedrine group and 3 ml saline wat er at control group. After legs were laid down on the lithotomy position, variab les of SBP, MBP and P were recorded in ten minutes. RESULTS: Dur ing ten minutes after double legs were laid down, the variables were lightly ris en about 8.7 % to 76.9 % in ephedrine group and were fallen about 7.8 % to 85.7 % in control group. The difference on variables of two groups was significant (P
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Objective: To determine the value of telomerase activity in urine exfoliated cells as clinical indicator of tumor presence, stage, and recurrence. Methods: The techniques of TRAP-PCR and TRAP-sliver staining were employed to detect telomerase activity in 73 patients with TCC before operation (study group) and 20 benign urothelial cancer patients (control group) and 21 normal individuals (normal group). Cytologic results were obtained simultaneously. The bladder tumor specimens were obtained from 73 patients during operation, and histologically evaluated for tumor content and grade. Results: Positive rate of telomerase activity detection in TCC patients (80.8%,59 of 73) was significantly higher than that of cytological examination (20.5%, 15 of 73). Positive telomerase activity was not found in 17 of 20 in control group and none was found in normal group. Analysis of the distribution of abnormalities with tumor stage revealed greater detection of high pathological stage (T 2-T 4) (89.7%, 26 of 29) compared with low stage (Tis-T 1) (75%, 33 of 44). Conclusion: Detection of telomerase activity in urine exfoliated cells may be a sensitive and effective marker in the diagnosis of TCC.