Adenocarcinoma ; pathology ; Carcinoma in Situ ; pathology ; Digestive System Neoplasms ; classification ; pathology ; Esophagogastric Junction ; pathology ; Humans ; Liver Neoplasms ; pathology ; Neoplasm Staging ; Neuroendocrine Tumors ; classification ; pathology ; Pancreatic Neoplasms ; pathology ; Precancerous Conditions ; pathology ; World Health Organization

Cough ; diagnosis ; Disease Management ; Humans

Objective To evaluate the value of increased threshold of SUVmax and delayed imaging on diluted and filled bladder for improving the detection of bladder cancer with 18F-FDG PET/CT.Methods From July 2007 to October 2012,18 F-FDG PET/CT was performed on 63 suspected or treated (with bladder preserved) bladder cancer patients (55 males,8 females,average age 69.1 years).After routine imaging,all patients were given 1 500-2 000 ml of water orally three times and voided three times.Then they underwent delayed pelvic imaging at a full bladder status.The routine images were reanalyzed with increased SUVmax threshold (from 6-8 to 8-20).The final diagnosis was confirmed by pathology or follow-up (＞6 months).The differences of SUVmax in urine,18 F-FDG metabolism in lesions between routine and delayed imaging were compared.Paired t test was used to compare their differences.Results The SUVmax of urine on routine and delayed imaging was 15.11±11.11 and 4.73±2.00 respectively (t=4.15,P＜0.01).Among the 63 patients,there were 15 malignant and 3 benign cases confirmed by pathology,and 45 patients without obvious abnormality during follow-up.All 18 cases were detected by 18F-FDG PET/CT including the 3 benign false positive cases (2 were positive by CT though negative by PET,and 1 FDG-avid cystitis).All 15 true positive cases were confirmed as primary or recurrent bladder carcinoma and 1 false positive case as inflammation.The detection rates of early imaging with routine and increased display threshold of SUVmax were 18.8％(3/16) and 43.8％(7/16),respectively.Conclusion Increased SUVmax threshold for display and delayed imaging with diluted urine under full bladder status could effectively improve the detection rate of primary or recurrent bladder cancer with 18F-FDG PET/CT.

Objective To investigate the distribution,drug resistance characteristics and genotypes of extended-spectrum-lactamases (ESBLs)-producing strain in pathogenic gram-negative rod in infection of newborn in Guangzhou.Methods The standard was performed by the production for ESBLs by phenotypic screening and confirmatory test provided by the National Committee for Clinical Laboratory Standards in 2001.The method of polymerase chain reaction(PCR) amplification was perbonmed and DNA sequences were analyzed by ESBLs gene sequencing.Results Total of 71 un-repicated and consecutive Gram-negative bacilli were isolated from 13 hospitals in Guangzhou,and the prevalence of ESBLs-producing clinical Gram-negative isolates was 59.2%(42/71).The PCR results showed that most pathogenic bacilli which infected newborn could be separated two or more genes of ESBLs.The type of TEM,SHV,CTX-M1,CTX-M9,OXA was 35.6%, 26.7% ,10.9%,24.8%,2.0%,respectively.The result of drug resistance monitoring showed that pathogenic gram-negative bacillui which infected newborn were Escherichia coli and Klebsiella pneumonia mostly.Most parts of them were drug fast and even multidrug resistant to the commonly used antibiotics.The sensitive drugs were lmipenem(the rate of sensitivty 100%),cefoperazone/sulbactam(87.3%),piperacillin/tazbatam(85.3%),ceftazidime(82%),aztreonam(82%),cefepime(81.8%).Conclusions In Guangzhou,the incidence rate of ESBLs-producing strain are very high inpathogenic bacilli which infected in newborn and is multidrug resistance.The genetypes of produced ESBLs are TEM,SHV,CTX-M1,CTX-M9,OXA.

OBJECTIVETo investigate the dynamic changes of neurofilament contents in rat's spinal cord induced by 2, 5-hexanedione (2, 5-HD), and explore the molecular mechanism of n-hexane neuropathy.

METHODSMale Wistar rats were administered at a dosage of 400 mg/kg/day 2, 5-HD for 2, 4 and 8 weeks respectively. HD-induced neurological defects were detected and quantified using gait score, and the relative lev-els of NF-H, NF-M, and NF-L in spinal cords of rats were determined by Western Blotting.

RESULTSExposure to 2, 5-HD produced progressive gait abnormalities, which suggested that the rat model of 2, 5-HD-induced neurotoxicity was established successfully. Western-Blotting results showed that NFs content in spinal cord demonstrated a progressive decline as the intoxication continued. In the supernatant fraction, compared to the controls, NF-H con-tent decreased by 15.7%, 57.0%, and 58.0% respectively after 2, 4, and 8-week treatment with 2, 5-HD (P < 0.01); accordingly, NF-M decreased by 36.0%, 61.3%, and 65.2% respectively (P < 0.01); NF-L decreased by 20.8%, 43.9%, and 44.3% respectively (P < 0.01). In the pellet fraction, the contents of NF-H in groups of 4 and 8 weeks' exposure to HD decreased by 35.6% and 43.2%, respectively (P < 0.01), and those of NF-L decreased by 26.4% and 42.1%, respectively (P < 0.01) when compared to the control. Further-more, NF-M contents in groups of 2, 4 and 8 weeks' exposure decreased by 23.3%, 33.9%, and 63.7% respectively (P < 0.01). The NFs level in spinal cords was highly correlated with gait abnormality of treated rats as the intoxication went on. Multiple correlation coefficients of NF-H, NF-M, and NF-L content with gait score of HD-treated rat were 0.8912, 0.9282 and 0.8981 (P < 0.01) respectively.

CONCLUSIONThe declines of NFs are high-ly related to neurobehavioral abnormality of 2, 5-HD-treated animals, and involved in the development of n-hexane neuropathy.

Animals ; Disease Models, Animal ; Gait ; drug effects ; Hexanones ; toxicity ; Male ; Neurofilament Proteins ; metabolism ; Rats ; Rats, Wistar ; Spinal Cord ; drug effects ; metabolism

OBJECTIVETo investigate the effects of 50 Hz magnetic fields (MF) on DNA double-strand breaks in human lens epithelial cells (hLECs).

METHODSThe cultured human lens epithelial cells were exposed to 0.4 mT 50 Hz MF for 2 h, 6 h, 12 h, 24 h and 48 h. Cells exposed to 4-nitroquinoline-1-oxide, a DNA damage agent, at a final concentration of 0.1 micromol/L for 1 h were used as positive controls.After exposure, cells were fixed with 4 % paraformaldehyde and for H2AX (gamma H2AX) immunofluorescence measurement. gamma H2AX foci were detected at least 200 cells for each sample. Cells were classified as positive when more than three foci per cell were observed. Mean values of foci per cell and percentage of foci positive cells were adopted as indexes of DNA double-strand breaks.

RESULTThe mean value of foci per cell and the percentage of gamma H2AX foci positive cells in 50 Hz MF exposure group for 24 h were (2.93 +/-0.43) and (27.88 +/-2.59)%, respectively, which were significantly higher than those of sham-exposure group [(1.77 +/-0.37) and (19.38+/-2.70)%, P <0.05], and the mean value of foci per cell and the percentage of gamma H2AX foci positive cells in 50 Hz MF exposure group for 48 h were (3.14 +/-0.35) and (31.00 +/-3.44)%, which were significantly higher than those of sham-exposure group (P <0.01). However there was no significant difference between 50 Hz MF exposure groups for 2 h, 6 h, 12 h and sham-exposure group for above two indexes (P >0.05).

CONCLUSION0.4 mT 50 Hz MF exposure for longer duration might induce DNA double-strand breaks in human lens epithelial cells in vitro.

Cells, Cultured ; DNA ; radiation effects ; DNA Breaks, Double-Stranded ; radiation effects ; DNA Damage ; radiation effects ; DNA Repair ; radiation effects ; Electromagnetic Fields ; Epithelial Cells ; metabolism ; radiation effects ; Humans ; Lens, Crystalline ; cytology

OBJECTIVETo explore the role of cyclin dependent kinase 5 (CDK5) in 2, 5-hexanedione (HD)-induced neuropathy.

METHODSThirty male Wistar rats weighted 200 approximately 240 g were divided randomly into three groups, i.e. control group, 200 mg/kg HD group and 400 mg/kg HD group (n = 10 for each group). HD was administered to rats by intraperitoneal injection at dosage of 200 or 400 mg/kg for 8 weeks (five times per week) to establish the intoxicated rats model. The relative contents of CDK5, p35 and p25 were determined in cerebrum, spinal cord and sciatic nerve of rats by Western Blotting.

RESULTSCompared with that of the control group rats, p35 contents were significantly decreased (P < 0.01) in the cytosolic fractions of cerebrum and spinal cord in both the 200 and 400 mg/kg HD intoxicated rats, while in the membrane fractions of spinal cord and sciatic nerve, p35 contents were increased significantly (P < 0.01). The changes of p25 showed the same pattern with p35. P25 contents were significantly reduced (P < 0.05) in the cytosolic (cerebrum and spinal cord) and membrane (cerebrum) fractions of both HD-treated rats and were elevated (P < 0.01) in the membrane fraction of spinal cord and cytosolic fraction of sciatic nerve. The relative amounts of CDK5 were significantly decreased (P < 0.01) in the cytosolic and membrane fractions of cerebrum in both the 200 and 400 mg/kg HD intoxicated rats. Except for membrane fraction of sciatic nerve, the significant increased (P < 0.01) of CDK5 were observed in the spinal cord and sciatic nerve of both the 200 and 400 mg/kg HD treated rats.

CONCLUSIONHD can induce significant changes of CDK5 and its activators p35, p25 in nerve tissues, which may be related to the neuropathy induced by HD.

Animals ; Cyclin-Dependent Kinase 5 ; metabolism ; Disease Models, Animal ; Hexanones ; poisoning ; Male ; Nerve Tissue ; metabolism ; Nervous System Diseases ; chemically induced ; Phosphotransferases ; metabolism ; Rats ; Rats, Wistar

New Chemical Entities (NCEs) development is a systematic long-term project that involves multiple disciplines. The translation research will help to build an advanced R&D system from the basic laboratory research, preclinical studies and clinical evaluation to clinical application of drug, for the purpose of shortening the R&D cycle and accelerate the launch of new drugs. In new drug R&D and its clinical application, drug disposition (absorption, distribution, metabolism, excretion, ADME) properties are important criteria for assessing drug-likeness of candidates. ADME evaluation of NCEs plays an important role in the translation research throughout innovative drug R&D process. Therefore, ADME evaluation at the early stage of drug design and development will be helpful to improve the success rate and reduce costs, and further access to safe, effective drugs.
Absorption ; Biological Transport ; Drug Design ; Drug Evaluation, Preclinical ; Pharmaceutical Preparations ; chemistry ; metabolism ; Pharmacokinetics ; Tissue Distribution ; Translational Medical Research

CYP2D6 is an important drug-metabolizing enzyme. The polymorphism of CYP2D6 leads to metabolism difference and the different reactions of drugs in the individuals and different races are normal phenomenon in clinical medication. CYP2D6*10 is an important subtype in Asian people and 51.3% Chinese are classified with this subtype. To obtain recombinant active CYP2D6*1/CYP2D6*10 in baculovirus system by optimizing coexpression with CYPOR, and detect their activity to catalyze dextromethorphan, three recombinants pFastBac-CYP2D6*1, pFastBac-CYP2D6*10 and pFastBac-CYPOR were constructed and transformed into DH10Bac cell to obtain the recombinant Bacmid-CYPOR, Bacmid-CYP2D6*1 and Bacmid-CYP2D6*10. And then the recombinant CYP2D6*1 and CYP2D6*10 virus were obtained by transfecting Sf9. Then homogenate protein activity was determined with dextromethorphan as substrate. The multiple of infection (MOI) and its ratio of recombinant CYP2D6 virus to CYPOR virus were adjusted by detecting the activity of the homogenate protein. The Km and Vmax are 26.67 +/- 2.71 micromol x L(-1) (n=3) and 666.7 +/- 56.78 pmol x nmol(-1) (CYP2D6) x min(-1) (n=3) for CYP2D6*1 to catalyze dextromethaphan. The Km and Vmax are 111.36 +/- 10.89 micromol x L(-1) (n=3) and 222.2 +/- 20.12 pmol x nmol(-1) (CYP2D6) x min(-1) (n=3) for CYP2D6*10 to catalyze dextromethorphan. There is significant difference between CYP2D6*1 and CYP2D6*10 for Vmax and Km (P < 0.01). The clearance ratio of CYP2D6*1 is 25.0 and the clearance ratio of CYP2D6*10 is 2.0. The expressed CYP2D6*1 and CYP2D6*10 are useful tools to screen the metabolism profile of many xenobiotics and endobiotics in vitro, which are benefit to understand individual metabolism difference.
Animals ; Baculoviridae ; enzymology ; genetics ; Catalysis ; Cells, Cultured ; Chromatography, High Pressure Liquid ; methods ; Cytochrome P-450 CYP2D6 ; genetics ; metabolism ; Dextromethorphan ; metabolism ; Isoenzymes ; metabolism ; NADPH-Ferrihemoprotein Reductase ; genetics ; metabolism ; Plasmids ; Recombinant Proteins ; genetics ; metabolism ; Spectrometry, Mass, Electrospray Ionization ; Spodoptera ; cytology ; virology ; Transfection

OBJECTIVETo investigate the effects of garlic oil (GO) against the peroxidation damage of rat nerve tissue and the peripheral motor neuropathy induced by 2, 5-HD.

METHODSMale Wistar rats were divided into four groups, with 10 in each group. The model group, and low and high doses of GO groups were administrated with 2, 5-HD (ip, 300 mg/kg), respectively; The control group was treated with sodium chloride, five times per week for six weeks. Pretreatment with GO gavaged (40 mg/kg or 80 mg/kg) started one week be-fore 2, 5-HD treatment, and lasted to the end of the experiment. Neurobehavioral indexes were examined at the zero, second and fourth week. At the end of the experiment, the scores of the gait, and the concentration of MDA and GSH, the level of TAOC and the ability of inhibition of.OH in cerebrum, spinal cord and sciatic nerve were examined.

RESULTSCompared with the zero week, except of the control group rats, the hind limb landing foot splay of three groups rats decreased by 44%, 50% and 49% at the fourth week, respectively without significant difference. The threshold value of balance in model, GO low and high doses groups rats decreased by 30%, 45% and 68% at the fourth week, respectively, and lower than the control group rats (P < 0.01). GO low and high doses groups rats showed the serious abnormality at the fourth week, before one week of the model group rats. The scores of gait of model, and GO low and high doses groups rats increased significantly compared with control group rats, and the GO high dose group rats were higher than model group rats (P < 0.05). Increase of the concentration of MDA, and decrease of the level of the ability of inhibition of.OH were induced by 2, 5-HD in cerebrum, spinal cord and sciatic nerve. The concentration of MDA increased, and the level of the ability of inhibition of.OH decreased (P < 0.05 or P < 0.01), respectively. The results showed that the concentration of MDA decreased, and the level of the ability of inhibition of.OH induced by GO in cerebrum, spinal cord and sciatic nerve increased, the concentration of MDA of GO low doses group rats decreased, the level of the ability of inhibition of.OH increased, the concentration of MDA of GO high doses group rats decreased (P < 0.01) respectively, and the level of the ability of inhibition of.OH increased (P < 0.01) in nerve tissue.

CONCLUSIONGO has antagonist effect on the 2, 5-HD induced peroxidation damage, but can not improve the function of the peripheral motor nerve, indicating that the lipid peroxidation does not play an important role in 2, 5-HD neurotoxicity.

Allyl Compounds ; pharmacology ; Animals ; Drug Antagonism ; Garlic ; chemistry ; Hexanones ; toxicity ; Lipid Peroxidation ; drug effects ; Male ; Nerve Tissue ; drug effects ; metabolism ; pathology ; Plant Oils ; pharmacology ; Rats ; Rats, Wistar ; Sulfides ; pharmacology