Benzene ; poisoning ; Chronic Disease ; Female ; Humans ; Middle Aged ; Occupational Diseases

AIM: To investigate the effects of propofol on the expression of tissue-type plasminogen activator (tPA) and matrix metalloproteinase 9 (MMP9) in the hippocampus and the cognitive function in neonatal rats.METHODS: The 7-day-old rats were randomly divided into 3 groups: the rats in control (CON) group were intraperitoneally injected with normal saline for 7 d;the rats in single dose of propofol anesthesia (SP) group were intraperitoneally injected with normal saline for 6 d and with propofol on the 7th day;the rats in repeated dose of propofol anesthesia (RP) group were intraperitoneally injected with propofol for 7 d.Blood glucose and blood gas analysis were tested in 6 rats of each group.The rats were randomly selected from each group to isolate the hippocampal tissues at 2 h, 24 h, 48 h, 72 h and 30 d after the last injection.The spatial learning and memory functions of the other rats aged 25 d were determined by Morris water maze.The morphological changes of the hippocampus were observed by HE staining and Nissl's staining.The expression of tPA and MMP9 at mRNA and protein levels was determined by RT-PCR and Western blot.RESULTS: Compared with group CON, the protein expression of tPA and MMP9 in RP group was significantly decreased at each time point, while no significant decrease was observed in SP group except at the time point of 24 h.Compared with CON group, the mRNA expression of tPA and MMP9 was down-regulated obviously in RP group, which was not significantly down-regulated in SP group.From the 3rd training day of Morris water maze beginning, the escape latency was prolonged, and the space exploration time and the number of crossing the original platform location were reduced in RP group compared with CON group and SP group, while no significant difference was observed between CON group and SP group.Compared with CON group, the number of nerve cells reduced and nerve cells arranged in disorder in the hippocampus in RP group.Moreover, the number of Nissl body decreased significantly and finally developed into neuronal degeneration and necrosis in RP group, and no significant difference between SP group and CON group was observed.CONCLUSION: Repeated dose of propofol anesthesia leads to long-term cognitive dysfunction in neonatal rats, which may be related to the down-regulation of tPA and MMP9 expression and destruction of normal morphology and function of neurons in hippocampus, whereas single dose of propofol anesthesia has no such effects.

Aim To investigate the role of matrix metalloproteinase-9 down-regulation in the learning and memory dysfunction induced by propofol treatment in rats.Methods 7-day-old SD rats were randomly divided into three groups(n=18):control group(NS group) and repeated doses of propofol group(RP group) was intraperitoneally injected with normal saline and propofol respectively for consecutive seven days, single dose of propofol group(SP group) were intraperitoneally injected with normal saline first for consecutive six days, and then injected with propofol on 7th day.The blood gas and glucose levels were monitored of six rats randomly selected from each group.Morris water maze was conducted to test the learning and memory functions of the remaining rats.The expression of MMP-9, BDNF and caspase-3 was detected by Western blot, and the hippocampal neuron apoptosis was determinated by TUNEL staining.Results Compared with NS group and SP group, the escape latency in RP group was prolonged significantly, exploration time and the number of crossing the platform in RP group were markedly decreased(P<0.05).The expressions of MMP-9 and mBDNF in RP group declined, but the expression of proBDNF and the ratio of proBDNF/mBDNF in RP group were higher than those in NS group and SP group(P<0.05).Compared with NS group and SP group, the number of apoptotic neurons and the expression of cleaved-caspase-3 in RP group were increased significantly, but the expression of pro-Caspase3 in RP group was reduced(P<0.05).There was no difference between SP group and NS group regarding all the results(P>0.05).Conclusions Repeated exposure to propofol can lead to a decline in long-term learning and memory functions in neonatal rats, which may be related to the down-regulation of MMP-9 expression, proBDNF and mBDNF conversion disorder in hippocampus and the apoptosis of hippocampal neurons.However, single exposure to propofol has no significant effect.

A chiral high-performance liquid chromatography method was developed for the simultaneous determination of ibuprofen enantiomers in dog plasma. It was used to study the pharmacokinetics in the Beagle dog after intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen. Ketoprofen was chosen as the internal standard. After a simple precipitation using methanol as the precipitating solvent, both analytes and IS were separated on a Kromasil 100-5CHI-TBB chiral column (250 mm x4.6 mm, 5 μm) with isocratic elution using acetonitrile - 20 mmol x L(-1) phosphate buffer (pH 3.0, containing 5% methanol) (6 : 4) as the mobile phase. The detection wavelength was 220 nm. Liner calibration curves for both of the ibuprofen enantiomers were over the concentration range from 0.5 to 50 μg x mL(-1) with a lower limit of quantification of 0.5 μg x mL(-1), the accuracies were all in standard ranges. The intra- and inter- assay precisions were all below 7%. The recovery rate was 93.1% to 100.4%. The experiments proved that the method was simple, rapid and sensitive. It can be used in the quantitative determination of ibuprofen enantiomers in dog plasma. The method was used to determine the concentration of ibuprofen enantiomers in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen (9 mg x kg(-1)) and the pharmacokinetics parameters were calculated based on the concentration-time curves. The C(max) of S-ibuprofen in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen were 30.8 ± 4.7, 46.1 ± 5.9 and 20.0 ± 2.6 μg x mL(-1), respectively. In terms of the exposure of active ingredient, it revealed a significant difference between the administration of S-ibuprofen and the other two groups. The systematical R- to S- chiral inversion was discussed. Comparing the pharmacokinetic parameters at different doses, chiral inversion were 70.1% ± 36.6% and 76.4% ± 36.2%, respectively, after intravenous administration of racemic- and R-ibuprofen. This study provides a theoretical basis for the safety of ibuprofen formula of injection drug.
Animals ; Chromatography, High Pressure Liquid ; Dogs ; Ibuprofen ; blood ; pharmacokinetics ; Stereoisomerism

Complex genetic variation has been known to occur during the transmission of human enterovirus (HEV), and the HEV virulence and pathogenicity enhanced by genetic recombination also pose a serious threat to human health. In recent years, the interest in recombination mechanism of genetic plasticity has been renewed with the emergence of pathogenic recombinant circulating vaccine-derived polioviruses, which were implicated in poliomyelitis outbreaks in several regions of the world with insufficient vaccination coverage. This paper reviews recent research progress in HEV genome, including evolutionary characteristics, recombination types, and in vitro recombinant construction.
Animals ; Biomedical Research ; trends ; Enterovirus ; classification ; genetics ; Enterovirus Infections ; virology ; Humans ; Recombination, Genetic ; Viral Proteins ; genetics

AIM: To observe the role of c-fos in the protection by cholecystokinin-octapeptide (CCK-8) against pulmonary artery smooth muscle cell (PASMC) injury induced by lipopolysaccharide (LPS). METHODS: The ultrastructure of PASMC was observed under transmission electron microscope (TEM). MDA content,LDH release and the rate of trypan blue in PASMC were measured,and immunocytochemistry technique was adopted to observe the c-fos protein expression. RESULTS: The TEM results showed significant PASMC structural injury in LPS group and alleviated structural changes in LPS+CCK-8 group. CCK-8 reduced the increase in the rate of trypan blue uptake,MDA content and LDH release in PASMC induced by LPS. LPS lightly increased c-fos protein expression,which was enhanced by CCK-8. CONCLUSION: CCK-8 attenuated the injury of PASMC induced by LPS,which may be concerned with the increase in c-fos protein expression.

Objective To study expressions of heme oxygenase-1 mRNA and protein in rat hippocampus after hypoxic-ischemia brain damage(HIBD) as well as the relationship with apoptosis in brain.Methods Seven-day-old SD rats were randomly divided into hypoxic-ischemia brain damage group and sham control group.Expressions of HO-1 protein and mRNA as welll as the relationship with apoptosis after HIBD in neonatal rat were determined by immunohisochemistry and in situs hybridizaion as well as terminal deoxynucleotidy transferase mediated UTP-biotin nick end labeling(TUNEL).Results 1.In the right hippocampus,expression of HO-1 gene increased sharply at 4 h (P

Objective To investigate the stability of immunophenotyping in the course of relapse or at treatment failure of patients with acute lymphoblastic leukemia(ALL) and that of immunophenotyping of positive minimal residual disease(MRD).Methods From Aug.2000 to Dec.2007,33 children with ALL who relapsed or treated failure were enrolled. These children were detected MRD by flow cytometry. The immunophenotyping of children who relapsed or treated failure were compared with that of initial therapy;the immunophenotyping of MRD relapsed was compared with that of initial therapy.Results 1.In 23 out of 27 cases (85.18%) with B-ALL,changed at least 1 antigen between diagnosis and relapse.Six children with CD45 down-modulation and 2 children with CD45 up-modulation.Two children with CD19 down-modulation and 1 child with CD19 up-modulation.Six children with CD34 down-modulation and 4 children with CD34 up-modulation. Five children with CD10 down-modulation and 7 children with CD10 up-modulation.2.Six children with T-ALL had the same expression in CD45 between relapse and treatment failure. 3.These were 15 children had the least 1 case MRD,25 cases MRD were detected,these was 1 case up-modulation in CD45,1 case down-modulation in CD19,2 cases up-modulation and 8 cases down-modulation in CD34,3 cases up-modulation and 6 cases down-modulation in CD10.Conclusions Immunophenotyping of children with ALL may change at relapse and treatment failure. The frequency of change in B-ALL is higher than that of in T-ALL,but the change can not impact the detection of MRD.

Some clinical trials showed that the efficacy of traditional Chinese medicine was not good as the efficacy of western medicine even thoush clinical doctors have been using traditional medicine effectively. Such a result originated from improper application of western medical thoughts in routine clinical efficacy evaluation. To find differences from effective cases with non-effective cases and put the differences into the indication of next clinical trial would conform to the differentiation theory in traditional Chinese medicine. The differences, whether positively or negatively related to the efficacy, could be obtained from all information including symptom evaluation, tongue appearance, pulse feeling and biological parameters with non-linear and other statistical methods. More specific indication finding would be the key task for clinical efficacy evaluation via multiple clinical trials.
Clinical Protocols ; Clinical Trials as Topic ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Phytotherapy ; Treatment Outcome

Syndrome and formulae (or prescription) are two key issues in traditional Chinese medicine (TCM) and the premise research for material basis of TCM. However, vagueness of syndromes and complexity of formulae greatly limited the evaluation to syndromes and effective substance basis of prescription. Therefore, how to solve the evaluation of syndromes, confirming the efficacy material basis in prescription are the current hot issues of international concern. To solve these problems, establishing chinmedomics by integrated serum pharmacochemistry of TCM with metabolomics technology, that is a unique method of TCM research, made outstanding contributions in solving international concerns such as the effectiveness and security aspects of TCM. On the basis of the biological characterization of syndrome, the metabolic profiling of animal models of TCM syndrome, and related metabolic fingerprints as well as metabolic biomarkers were established to evaluate the overall effects of TCM formulae and corresponding relationship of syndrome-formulae. The active constituents were screened using the plotting of correlation between (endogenous) marker metabolites and (exogenous) serum constituents (PCMS), and is ongoing verification by further biological experiments. Correlation analysis between the ingredients in the body after oral formulae and endogenous markers in vivo can be used to clarify the active ingredients and synergistic properties. This method was successfully applied for rapid discovery of potentially bioactive components and metabolites from TCM, and through a series of studies on the chinmedomics, it proved that the established method could help to explore the effective substance for further research of TCM. As a new research approach, Chinmedomics is the best method to fit the holistic concept of TCM, and it can not only interpret the essence of syndrome but also elucidate the scientific connotation of Chinese medical formulae.
Animals ; Diagnosis, Differential ; Drug Prescriptions ; Drug Therapy ; Drugs, Chinese Herbal ; analysis ; pharmacokinetics ; Humans ; Medicine, Chinese Traditional