ObjectiveTo study the relationship between 18F-FDG uptake and tumor cell density,glucose transporter expression,cellular proliferation and angiogenesis before and after radiotherapy in C6 glioma rats.MethodsThirty C6 glioma-bearing male SD rats were randomly divided into three groups:A,B and C ( 10 rats in each group).Two weeks later,18F-FDG PET/CT was performed in group A.In groups B and C,18 F-FDG PET/CT was performed at 48 h and 1 week after radiotherapy,respectively.The ratio of SUVmax of tumor to muscle (T/M) was calculated.HE staining,immunohistochemical staining and Western blot were used to measure tumor cell density,Ki67 labeling index ( LI),microvessel density ( MVD),Glut-1 and VEGF expression quantitatively.The one-way analysis of variance and bivariate correlation analysis were used to compare the changes of each indicator and evaluate the correlation between T/M and biological indicators,respectively.Results Significant differences of T/M,tumor cell density,Ki67 LI,MVD,Glut-1 and VEGF among groups A,B and C were observed ( F =6.77,60.66,104.56,95.49,9.13,24.48,respectively,all P ＜0.05).Least significant difference (LSD) test showed that there was no significant difference between group A and B in T/M,tumor cell density and Ki67 LI ( 10.86 ± 3.31,730.50 ± 78.93,20.02 ± 2.14 vs 9.23 ± 4.56,672.70 ± 92.98,18.56 ± 2.26).However,the indicators of group C (5.16 ± 2.52,355.60 ± 72.62,7.81 ± 1.76 ) were significantly decreased compared with those of groups A and B (all P ＜0.05 ).MVD and Glut-1 expression of group B increased slightly compared with those of group A ( 19.50 ± 1.96,0.20 ± 0.09 vs 17.90 ± 2.02,0.15 ± 0.04),but the difference was not statistically significant.Nevertheless,the two indicators were significantly decreased in group C ( 8.40 +1.84 and 0.07 ±0.06,P ＜0.05).VEGF expression in group B (0.42 ±0.13) was significantly higher than that in groups A and C (0.17 ±0.04 and 0.16 ± 0.09) ( both P ＜ 0.05 ).The changes of T/M were positively correlated with the changes of tumor cell density between groups A and B ( r =O.81,P ＜ 0.05 ).Changes of T/M were positively correlated with the changes of tumor cell density,Ki67 LI,MVD and Glut-1 between groups A and C (r =O.83,0.71,0.68,0.62,all P ＜ 0.05 ).ConclusionsThe changes of 18 F-FDG uptake in C6 glioma rats were only correlated to the changes of tumor cell density at 48 h after radiotherapy.However,the changes of 18F-FDG uptake closely correlate to the changes of a variety of biological indicators at 1 week post radiotherapy.

Objective To investigate the correlation between ~(18)F-fluorodeoxyglucose (FDG) uptake and hypoxia inducible factor1α (HIF-1α) level,microvessel density (MVD) in human gliomas.Methods ~(18)F-FDG PET scan was performed preoperatively in 41 patients with gliomas (including 23 highgrade and 18 low-grade tumors).The ratios of maximum standardized uptake value(SUV_(max))between tumor (T)and contralateral white matter (WM) were calculated (T/WM).Immunohistochemical stain methods were used to evaluate the level of HIF-1α and measure the MVD in tumors.Correlation analysis between SUV_(max) of T/WM and HIF-1α level,MVD wag performed.The t-test,one-way ANOVA test,Spearman rank correlation and Wilcoxon signed-rank test were calculated using SPSS 11.5 software.Results (1)The SUV_(max) of T/WM,HIF-1α level and MVD in high-grade and low-grade tumors groups were 3.39±1.43,95.7% and 44.13±16.1 vs 1.46±0.55.55.6% and 18.83±7.07,respectively.The difierences of SUV_(max) of T/WM,HIF-1α level and MVD between two groups were statistically significant (t=-5.921,z=-3.938,t=-6.745,all P＜0.05).(2)Among 41 gliomas,the strong positive expression of HIF-1α was observed in 8,mederate in 9,weak in 15 and negative expression was found in 9,SUV_(max) of T/WM and MVD increased with increasing HIF-1α level.The differences of SUV_(max) of T/WM and MVD among 4 different groups were statistically significant (F=7.41,P＜0.05).(3) The MVD of all gliomas was ranged from 9.76 to 94.52,which correlated with SUV_(max) of T/WM(r=0.759,P＜0.05).Conclusions The SUV_(max) of T/WM correlates with HIF-1α level and MVD in gliomas.Therefore,~(18)F-FDG PET provides preoperatively a noninvasive assessment of hypoxia or angiogenesis in human glionma.

A colistin producing strain Paenibacillus polymyxa AS1.541 was treated by N-methyl-N-nitro-N-nitrosoguanidine(NTG) for increasing yields of the antibiotic colistin.High-yield strains were obtained by selection of deregulated mutant which grow on media containing colistin,a self second metabolite,and ethionine,an analogue of methionine.Some of these mutants have higher yield of colistin than that of the parent strain.

Enterohemorrhagic Escherichia coli ; Escherichia coli Infections ; epidemiology ; Germany ; epidemiology ; Humans

Panax notoginseng (PN) is one of the commonly used clinical medicines for cardiovascular diseases and possesses a variety of pharmacological effects. P. notoginseng saponins (PNS) are the most important bioactive components in PN. The purpose of this study was to explain the mechanism of PNS on molecular network level. 18 targets of the main medicinal ingredients of PNS were gained by virtual screening based on pharmacophores and data mining. A protein interaction network of PNS was constructed with 189 nodes and 721 interactions. By a graph theoretic clustering algorithm Molecular Complex Detection (MCODE), 14 modules were detected. Gene ontology (GO) enrichment analysis of the modules demonstrated that the roles of PNS played in cardiovascular disease related to multiple biological processes, which could represent the characteristics of traditional Chinese medicine (TCM) as a whole to regulate the disease. The results showed that the blood circulation and hemostasis efficacy of PN related with the biological processes such as positive regulation of cAMP metabolic and biosynthetic process, platelet activation and regulation of blood vessel size, regulation of T cell proliferation and differentiation and so on. Therefore, the module-based network analysis will be an effective method for better understanding TCM.
Drugs, Chinese Herbal ; chemistry ; Humans ; Panax notoginseng ; chemistry ; Protein Interaction Maps ; drug effects ; Proteins ; chemistry ; Saponins ; chemistry

OBJECTIVETo investigate the pharmacokinetic and distribution character of scutellarin in plasma and tissues in rats, in order to provide some references for rational drug use in the clinic.

METHODThe solution of scutellarin was administered to rats (80 mg x kg(-1)) by oral gavage. A high performance liquid chromatography method determinated the scutellarin concentration in rat plasma and tissue. The plasma samples were performed by solid phase extraction method. The other biological samples were extracted by ethyl acetate.

RESULTThe range of scutellarin in plasma and tissue in rats were 10-1280 ng x mL(-1) (R2 > 0.99), 40-1280 ng x g(-1) (R2 > 0.99), respectively. The lowest detection of scutellarin were 10 ng x mL(-1) and 40 ng x g(-1), the precision were less than 8%. The main pharmacokinetic parameters of scutellarin were as follows: tmax, Cmax, AUC and MRT being (7.7 +/- 0.9) h, (288.0 +/- 75.2) microg x L(-1), (5.6 +/- 1.6) microg x mL(-1) x h(-1), (17.5 +/- 1.4) h(-1), respectively.

CONCLUSIONThese methods applied the study of pharmacokinetics of scutellarin. After oral the scutellarin in rats, the concentration-time course doesn't obey any compartment model. The concentration-time curve is the double peaks.

Animals ; Apigenin ; blood ; isolation & purification ; pharmacokinetics ; Area Under Curve ; Chromatography, High Pressure Liquid ; Female ; Glucuronates ; blood ; isolation & purification ; pharmacokinetics ; Male ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution

Veratridine, a blocker of inactive gate of sodium channel, was used to perfuse L5 dorsal root ganglion (DRG) topically. Afferent activities of type A single fiber from these DRGs were recorded. It was found that after a 10-min bath of veratridine (1.8-3 micromol/L), some of the primary silent DRG neurons were triggered by touch or pressure on the receptive fields or by electrical stimulation of the sciatic nerve to produce high-frequency firing, which was termed triggered oscillation presenting a U-type of interspike intervals (ISI) or other types of oscillations. The longer the intervals between stimulating pulses, the more stimulating pulses were needed to trigger the oscillation. The oscillation, triggered by electric stimuli with different duration or patterns, had no significant difference in their patterns. The duration of the inhibitory period after a triggered oscillation was generally 30-90 s. It was also observed that this kind of triggered oscillation was induced by afferent pulses of the same neurons. These results suggest that triggered oscillation, which may contribute to the fit of triggered pain, can be produced in primary sensory neurons after application of veratridine.
Action Potentials ; physiology ; Animals ; Female ; Ganglia, Spinal ; cytology ; drug effects ; Male ; Neurons, Afferent ; physiology ; Rats ; Rats, Sprague-Dawley ; Sodium Channel Blockers ; pharmacology ; Veratridine ; pharmacology

OBJECTIVETo study the mutagenicity and teratogenicity induced by ammonium dinitramide(ADN).

METHODSAccording to technical specifications for toxicity determination of chemicals, Salmonella typhimurium reverse mutation assay (Ames assay), in vivo mammalian erythrocyte micronucleus test, sperm malformation test and teratogenesis test were used to detect the mutagenicity and teratogenicity induced by AND.

RESULTSWhen the exposure doses of AND were 8-5000 pg/plate, the result of Ames assay was negative. As compared with control group, the micronucleus rate of mice exposed to 113.8 mg/kg AND significantly increased(P<0.05), the sperm malformation rates of mice exposed to 54.4-272.0 mg/kg AND did not increased significantly. The survival rate of fetuses decreased, the rate of assimilated fetuses increased, the rate of fetus sternum agenesis enhanced in mice exposed to 319 mg/kg AND, as compared with controls. The rates of in the 4th-6th fetus sternum agenesis in groups exposed to 21.3, 79.7 and 319 mg/kg AND were higher than that in control group. The malformation rate of fetus bowels in groups exposed to 319 mg/kg AND was higher than that in control group. The teratogenic index of ADN was 30.

CONCLUSIONAND may be a mutagen and induce the teratogenic effect.

Animals ; Embryo, Mammalian ; drug effects ; pathology ; Female ; Male ; Mice ; Mice, Inbred Strains ; Micronucleus Tests ; Mutagenicity Tests ; Nitrites ; toxicity ; Pregnancy ; Quaternary Ammonium Compounds ; toxicity ; Spermatozoa ; drug effects ; pathology ; Sternum ; drug effects ; pathology

OBJECTIVETo study the acute, subacute and subchronic toxicity induced by ammonium dinitramide (ADN), and to ascertain the gradation and target organs of acute toxicity induced by AND.

METHODSAccording to technical specifications for toxicity determination of chemicals, the oral tests for acute, subacute and subchronic toxicity induced by AND were performed for 90 days.

RESULTSThe oral LDx for mouse and rat was 568.9 mg/kg and 616.6 mg/kg ADN respectively. The gradation of acute toxicity induced by AND was low level. The results of oral subacute and subchronic toxicity tests (for 28 and 90 days) showed that a gain in weight in group exposed to 123 mg/kg AND was significantly lower than that in control group (P<0.05), the TBIL and ALT in group exposed to 61.6 and 123 mg/kg AND significantly increased and the ratio of liver weight to body weight obviously decreased, as compared with control group, the number of animals with hepatic pathological changes in group exposed to 61.6 and 123 mg/kg AND was significantly higher than that in control group (P<0.05).

CONCLUSIONThe gradation of acute toxicity induced by ADN was low level. When the exposure dose of AND was 30.8 mg/kg, the adverse effect was not observed, and the target organ was liver.

Animals ; Body Weight ; Female ; Liver ; drug effects ; pathology ; Male ; Mice ; Mice, Inbred Strains ; Nitrites ; toxicity ; Quaternary Ammonium Compounds ; toxicity ; Rats ; Rats, Sprague-Dawley ; Toxicity Tests, Acute ; Toxicity Tests, Subchronic

OBJECTIVETo study the 3, 4- dinitro-furazan-based oxidation furazan (DNTF) of sub-acute toxicity and chronic toxicity, to determine the acute toxicity classification DNTF, the nature of toxic effects and major target organ for the development provide the basis for occupational exposure limits.

METHODS( 1) Acute toxicity: The oral gavage method once infected, symptoms of poisoning of animals observed to calculate the LD50DNTF and 95% confidence limits. ( 2) sub-chronic experiment: selection of 96 healthy SD rats were randomly divided into four groups, doses of 25, 56.2, 125 mg/kg and the negative control group, Exposure for ninety days,five days a week, once a day, The rats were killed at end of Exposure, heart, liver, spleen, lung, kidney, brain,testis, uterus were taken to observe the pathological changes.

RESULTS( 1) Acute oral toxicity test results indicate that DNTF rat oral LD50 greater than 5000 mg/kg, DNTF mice treated by oral LD50 4589 mg/kg, 95%confidence limit for the 4026-5230 mg/kg, Acute toxicity grade level is low toxicity compounds. (2) Sub-chronic toxicity experiment, the high-dose male rats, high, medium and low-dose group female rats weight gain than the negative control group, compared with the control group, the difference was statistically significant (P<0.05).125 mg/kg of serum alanine aminotransferase, aspartate aminotransferase was significantly higher. 125 mg/kg dose groups, liver, kidney, lung, testicular factor was significantly higher. Liver, kidney, lung histological examination showed obvious morphological changes.

CONCLUSIONAcute toxicity grade DNTF low toxicity level compounds, target organ toxicity of liver, kidney and lung.

Animals ; Female ; Lethal Dose 50 ; Male ; Mice ; Nitrofurazone ; analogs & derivatives ; toxicity ; Oxadiazoles ; toxicity ; Rats ; Rats, Sprague-Dawley ; Toxicity Tests