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.

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.

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

OBJECTIVETo evaluate the value of (18)F-FDG and (11)C-MET PET-CT scan in differentiation of brain ringlike-enhanced lesions on MRI imaging.

METHODSForty-one brain ringlike-enhanced lesions on MRI imaging including 30 brain tumors and 11 non-neoplastic lesions confirmed pathologically or clinically underwent (18)F-FDG and (11)C-MET PET-CT brain scan. Among them, 15 patients who were suspected to have brain metastasis received body scan by (18)F-FDG PET-CT. Both images were analyzed visually and semi-quantitatively.

RESULTSVisual analysis: for brain tumors the diagnostic sensitivity, specificity and accuracy of (18)F-FDG PET-CT was 53.3%, 72.7%, 58.5%, versus 96.7%, 90.9%, 95.1% of (11)C-MET PET-CT, respectively. All the primary foci in 9 patients with brain metastases were detected by body (18)F-FDG PET-CT scan. Semiquantitative analysis: There was a significant difference in the uptake between highly differentiated malignant and poorly differentiated tumors as well as non-neoplastic lesions for both tracers (P < 0.01), while between low-grade malignant tumors and non-neoplasm lesions, there was a difference in uptake only by (11)C-MET (P < 0.01). No significant difference between the uptakes in brain metastasis and glioblastomas was found by both tracers (P > 0.05).

CONCLUSIONBoth (18)F-FDG and (11)C-MET PET-CT are useful in differentiation of brain ringlike-enhanced lesions on MRI imaging. (11)C-MET PET-CT is more helpful than (18)F-FDG PET-CT in differential diagnosis of low-grade neoplastic from non-neoplastic lesions. Combination of (18)F-FDG and (11)C-MET PET-CT scans can improve the accuracy of differential diagnosis for brain ringlike-enhanced lesions on MRI imaging.

Acetates ; Adolescent ; Adult ; Aged ; Brain Abscess ; diagnosis ; Brain Neoplasms ; diagnosis ; pathology ; secondary ; Carbon ; Carbon Radioisotopes ; Child ; Craniopharyngioma ; diagnosis ; pathology ; secondary ; Diagnosis, Differential ; Female ; Fluorodeoxyglucose F18 ; Glioblastoma ; diagnosis ; pathology ; secondary ; Humans ; Lung Neoplasms ; diagnosis ; pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pituitary Neoplasms ; diagnosis ; pathology ; secondary ; Positron-Emission Tomography ; methods ; Radiopharmaceuticals ; Sensitivity and Specificity ; Young Adult

OBJECTIVEThe exercise rehabilitation in patient with chronic heart failure (CHF) is standard clinical practice, but it is rare using CardioPulmonary Exercise Testing (CPET) guide to prescribe exercise rehabilitation in China.

METHODSWe performed symptom limited maximal CPET in 10 patients with CHF, randomly divided into two groups: 5 patients as control without exercise and 5 exercise patients used Δ50%W intensity to exercise 30 min/d, 5 d/w, x12 w. Before and after 12 w rehabilitation, we evaluated functions.

RESULTSThere were no significant difference between two groups patients (P > 0.05). The exercise duration was increased from 8 min to 23 min after rehabilitation (P < 0.001); distance 6 minutes walking was increased from 394 m to 470 m (P < 0.05); score of Minnesota quality of life was decreased from 25 to 3 in exercise group (P < 0.01). However, there were nosignificant changes in control group (P>0.05) and their changes were smaller than those in exercise group (P < 0.01).

CONCLUSIONThe CPET guiding exercise rehabilitation is safe and effective for patients with CHF.

China ; Chronic Disease ; Exercise Test ; Exercise Therapy ; Heart Failure ; therapy ; Humans ; Quality of Life ; Walking

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