RESUMO
Objective: To investigate the antimicrobial resistance of food-borne diarrheagenic Escherichia coli (DEC) and the prevalence of mcr genes that mediates mobile colistin resistance in parts of China, 2020. Methods: For 91 DEC isolates recovered from food sources collected from Fujian province, Hebei province, Inner Mongolia Autonomous Region and Shanghai city in 2020, Vitek2 Compact biochemical identification and antimicrobial susceptibility testing platform was used for the detection of antimicrobial susceptibility testing (AST) against to 18 kinds of antimicrobial compounds belonging to 9 categories, and multi-polymerase chain reaction (mPCR) was used to detect the mcr-1-mcr-9 genes, then a further AST, whole genome sequencing (WGS) and bioinformatics analysis were platformed for these DEC isolates which were PCR positive for mcr genes. Results: Seventy in 91 isolates showed different antimicrobial resistance levels to the drugs tested with a resistance rate of 76.92%. The isolates showed the highest antimicrobial resistance rates to ampicillin (69.23%, 63/91) and trimethoprim-sulfamethoxazole (59.34%, 54/91), respectively. The multiple drug-resistant rate was 47.25% (43/91). Two mcr-1 gene and ESBL (extended-spectrum beta-lactamase) positive EAEC (enteroaggregative Escherichia coli) strains were detected. One of them was identified as serotype of O11:H6, which showed a resistance profile to 25 tested drugs referring to 10 classes, and 38 drug resistance genes were predicted by genome analysis. The other one was O16:H48 serotype, which was resistant to 21 tested drugs belonging to 7 classes and carried a new variant of mcr-1 gene (mcr-1.35). Conclusion: An overall high-level antimicrobial resistance was found among foodborne DEC isolates recovered from parts of China in 2020, and so was the MDR (multi-drug resistance) condition. MDR strains carrying multiple resistance genes such as mcr-1 gene were detected, and a new variant of mcr-1 gene was also found. It is necessary to continue with a dynamic monitoring on DEC contamination and an ongoing research into antimicrobial resistance mechanisms.
Assuntos
Infecções por Escherichia coli , Proteínas de Escherichia coli , Humanos , Colistina/farmacologia , Antibacterianos/farmacologia , Infecções por Escherichia coli/epidemiologia , Proteínas de Escherichia coli/genética , Farmacorresistência Bacteriana/genética , China/epidemiologia , Escherichia coli , Plasmídeos/genética , Testes de Sensibilidade MicrobianaRESUMO
Objective: To understand the antimicrobial resistance and genome characteristics of Campylobacter isolates recovered from retailed poultry meat samples in 20 provinces in China in 2020. Methods: In 2020, 265 Campylobacter strains including 244 Campylobacter jejuni and 21 Campylobacter coli collected from retailed poultry meat samples in China were tested for antimicrobial resistance to 9 antimicrobial compounds by using the agar dilution method. Forty-two selected isolates were sent for whole genome sequencing and 38 high-quality genomes were analyzed for their antimicrobial resistance genes, virulence genes, sequence types and genetic diversity. Results: The resistance rates of Campylobacter isolates from poultry meats to tetracycline, nalidixic acid and ciprofloxacin were the highest (84%-100%), with 53.2% of the isolates showing multidrug resistance in this study. The resistance rates of C. coli to erythromycin, azithromycin, telithromycin, gentamicin and clindamycin were significantly higher than those of C. jejuni (P<0.05). The resistance genes conferring resistance to ß-lactams (100%, 38/38), quinolones (94.7%, 36/38), tetracycline (81.6%, 31/38) and aminoglycosides (50%, 19/38) were the most frequently detected among 38 Campylobacter genomes. C. jejuni carried more virulence genes than C. coli. In total, 19 and 17 sequence types (ST) were obtained from 20 sequenced C. jejuni and 18 C. coli isolates, respectively, including 5 novel STs. The isolates showed a high genetic diversity based on their sequence types. Conclusion: The phenomenon of antimicrobial resistance in Campylobacter from poultry meat sources in China is relatively serious, and resistance and virulence genes are widely distributed in Campylobacter. There is genetic diversity in Campylobacter.
Assuntos
Antibacterianos , Campylobacter , Humanos , Animais , Antibacterianos/farmacologia , Campylobacter/genética , Aves Domésticas , Farmacorresistência Bacteriana/genética , Genômica , China , TetraciclinaRESUMO
Objective: To analyze the molecular characteristics of Listeria monocytogenes strains from ready-to eat food in China. Methods: A total of 239 Listeria monocytogenes strains isolated from ready-to-eat food in 2017, all strains underwent whole-genome sequencing (WGS) , and comparisons uncovered population structure derived from lineages, clonal complex, serogroups, antimicrobial susceptibility and virulence, which were inferred in silico from the WGS data. Core genome multilocus sequence typing was used to subtype isolates. Results: All strains were categorized into three different lineages, lineage â ¡ was the predominant types in food, and IIa was the main serogroups. CC8, CC101 and CC87 were the first three prevalent CCs among 23 detected CCs, accounting for 49.4%. Only 4.6% (11 isolates) of tested strains harbored antibiotic resistance genes, which were mostly trimethoprim genes (7 isolates, 2.9%). All strains were positive for LIPI-1, and only a part of strains harbored LIPI-3 and LIPI-4, accounting for 13.8% (33 isolates) and 14.2% (34 isolates), respectively. ST619 carried both LIPI-3 and LIPI-4. 51.5% (123 isolates) of strains carried SSI-1, and all CC121 strains harbored SSI-2. Different lineages, serogroups and CCs can be separated obviously through cgMLST analysis, and 24 sublineages were highly concordant with CCs. Conclusion: â ¡a was the main serogroups in ready-to-eat food isolates in China; CC8, CC101 and CC87 were the prevalent CCs, and CC87 isolates was hypervirulent isolates, cgMLST method can be adopted for prospective foodborne disease surveillance and outbreaks detection.
Assuntos
Microbiologia de Alimentos , Listeria monocytogenes/isolamento & purificação , Listeriose/microbiologia , China/epidemiologia , Humanos , Listeriose/epidemiologiaRESUMO
Objective: To investigate the etiological characteristics of Streptococcus pyogenes that caused scarlet fever from 2012 to 2016 in Tianjin. Methods: The subjects were children diagnosed clinically as scarlet fever in Tianjin scarlet fever monitoring hospital from 2012 to 2016. The exclusion criteria were children with scarlet fever who were unable to cooperate with sampling. A total of 575 cases of children's swabs were collected. Biochemical methods were used to isolate and identify the bacteria of pharynx swab, and the PCR method was used to detect the emm genotyping and superantigen speA and speC, and the resistance of the strains to 10 antibiotics was measured by K-B paper method. We compared the carrying status of superantigen genes by different types of GAS and the resistance of all GAS to different antibiotics. Results: There were 5 emm types (emm1/11/12/22/89). The dominant types were emm12 (52.9%, 100 strains) and emm1 (44.4%, 84 strains). The carrying rates of speA and speC genes were 21.7% (41 strains) and 76.7% (145 strains), respectively. The speA gene carrying rate of emm1 type GAS was 33.3% (28 strains), which were higher than that of emm12 (12% (12 strains)) (χ(2)=12.21, P<0.001). The speA and speC gene simultaneous carrying rate of emm1 type GAS was 27.4% (23 strains), which was higher than that of emm12 type (12% (12 strains)) (χ(2)=7.01, P=0.008). The percentages of the strains that were resistant to Azithromycin, Erythromycin, Clarithromycin, Clindamycin, Tetracyclin, Levofloxacin and Chloramphenicol were 96.8% (183 strains), 96.3% (182 strains), 92.1% (174 strains), 92.1% (174 strains), 73.0%(138 strains), 2.1% (4 strains) and 1.6% (3 strains), respectively. All isolates were susceptible to Penicillin, Cefazolin and Vancomycin, and there were statistical significance (χ(2)=953.28, P<0.001). Conclusion: The dominant emm types causing scarlet fever are emm12 and emm1. The frequencies of speA and speC in emm1 and emm12 are different. S.pyrogenes in Tianjin were susceptible to penicillin, cefazolin and vancomycin, but highly resistant to the clindamycin, clarithromycin, erythromycin and azithromycin.
Assuntos
Escarlatina/microbiologia , Streptococcus pyogenes/genética , Antibacterianos/farmacologia , Criança , China , Humanos , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/efeitos dos fármacos , Streptococcus pyogenes/isolamento & purificação , Superantígenos/genéticaRESUMO
Objective: To analyze liquid milk exposure of thiocyanate among Chinese population and preliminarily assess its health risk. Methods: A total of 2 059 raw milk samples were collected during 2013 and 2014 from 12 Chinese provinces, New Zealand and Netherlands. Farms were chosed according to the main sources of dairy companies, the distribution of farms and the yield of milk. Content of thiocyanate were detected by ion chromatography. Liquid milk consumption data were taken from Chinese beverage and alcoholic beverage consumption survey in 18 cities or counties in 9 provinces, including 16 775 subjects older than 3. A simple distribution model was used to estimate the exposure of thiocyanate from liquid milk. The tolerable daily intake (TDI) of thiocyanate was made 0.08 mg·kg(-1)·d(-1). Then the exposures of different age groups were compared with TDI. Results: Finally, 1 331 samples out of 2 059 were detected to contain thiocyanate. The detection rate was 65%. The average concentration of thiocyanate was 2.11 mg/kg, with a range of 0.10-16.20 mg/kg. The general population's consumption of thiocyanate by drinking liquid milk was 0.001 mg · kg(-1) · d(-1), which was lower than TDI. The P(95) of general population and consumers were 0.009 mg · kg(-1) · d(-1) and 0.020 mg·kg( -1)·d(-1) respectively, which were also lower than TDI. Mean exposures of population aged 3-6, 7-12, 13-17, 18-59 as well as elderly aged 60 and above were 0.007, 0.003, 0.002, 0.001 and 0.001 mg · kg(-1)·d(-1) respectively, which were all lower than TDI. Conclusion: The results suggested that the health risk of thiocyanate exposure by drinking liquid milk among Chinese population was at a low level. However, milk products for children deserve more concern.
Assuntos
Inocuidade dos Alimentos/métodos , Leite/química , Tiocianatos/química , Idoso , Animais , Povo Asiático , Criança , Humanos , Países Baixos , Nova Zelândia , Medição de RiscoRESUMO
Overviews were evaluated of tritium releases and related doses to the public from airborne and liquid effluents from nuclear power plants on the mainland of China before 2009. The differences between tritium releases from various nuclear power plants were also evaluated. The tritium releases are mainly from liquid pathways for pressurised water reactors, but tritium releases between airborne and liquid effluents are comparable for heavy water reactors. The airborne release from a heavy water reactor is obviously higher than that from a pressurised water reactor.
Assuntos
Contaminação Radioativa do Ar/estatística & dados numéricos , Resíduos Industriais/análise , Centrais Nucleares/estatística & dados numéricos , Monitoramento de Radiação/estatística & dados numéricos , Resíduos Radioativos/estatística & dados numéricos , Trítio/análise , Contaminação Radioativa da Água/estatística & dados numéricos , Contaminação Radioativa do Ar/análise , China , Resíduos Radioativos/análise , Contaminação Radioativa da Água/análiseRESUMO
This study focuses on the possible use of the spent corncob substrate (SCS), an agricultural waste used after the cultivation of white rot fungus Pleurotus ostreatus, to adsorb Methylene Blue (MB) from aqueous solutions. A batch adsorption study was carried out with variable solution pH, adsorption time, temperature and initial MB concentration. It was found that MB uptake was favorable at pH ranging from 4.0 to 12.0 and the equilibrium adsorption capacity can be reached promptly within about 180 min. The biosorption data were also calculated by the pseudo-second-order kinetic model and Langmuir isotherm model. Thermodynamic parameters show that the adsorption is a spontaneous and endothermic process. The study highlighted a new pathway to develop potential low-cost biosorbent for the removal of dye pollutants from wastewater.
Assuntos
Azul de Metileno/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Zea mays/química , Adsorção , Agricultura , Concentração de Íons de Hidrogênio , Cinética , Azul de Metileno/química , Soluções , Espectrofotometria Ultravioleta , Termodinâmica , Poluentes Químicos da Água/químicaRESUMO
Phenolic compounds bisphenol A (BPA) and 4-nitrophenol (4-NP) are the prime water contaminants. As reported, these compounds are some of the highly hazardous ones to the human and living species. In this study, T-ZnO-rGO-PEI composite was synthesized employing hydrothermal method and the obtained composite samples were systematically characterized by FTIR, XPS, FE-SEM and HR-TEM studies. The FTIR, XPS analysis confirmed the successful surface modification of T-ZnO-rGO-PEI composite. The FE-SEM morphology confirmed the formation of ZnO (arm length about 2.5 µm) tetrapod structured in synthesized T-ZnO-rGO-PEI composite. The thickness of formed ZnO arm (0.44 µm) was increased after the polymer coating which confirmed the successful surface modification by PEI polymer. The HR-TEM images confirm the uniform coating of PEI polymer on T-ZnO-rGO surface. The catalytic activity and adsorption capacity of the synthesized T-ZnO-rGO-PEI composite was successfully explored using 4-nitrophenol and bisphenol-A as model pollutants .T-ZnO-rGO-PEI composite and found that 4-NP reduction reaction was completed within 10 min with the rate of 0.224 min-1. The BPA adsorption over T-ZnO-rGO-PEI exhibited high adsorption rate of 0.0210 min-1. In addition, the detailed 4-NP reduction and BPA adsorption mechanism was demonstrated. Hence the synthesized T-ZnO-rGO-PEI composite is a promising catalyst for the removal of micropollutants in aqueous medium.
Assuntos
Grafite , Óxido de Zinco , Adsorção , Catálise , Cor , HumanosRESUMO
4- Nitrophenol (4-NP) is a top rated hazardous environmental pollutant and secondary explosive chemicals. For the sake of ecology and environment safety, the catalytic reduction and detection of 4-NP is highly important. In this work, ɤ-Fe2O3-nitrogen doped rGO (ɤ-Fe2O3-N-rGO) nanohydrogel was synthesized by green hydrothermal method. The morphology and phase purity of prepared ɤ-Fe2O3-N-rGO nanohydrogel were confirmed by various analytical (SEM, TEM, XRD, and XPS) and electrochemical techniques. The morphological structure of ɤ-Fe2O3-N-rGO nanohydrogel confirmed that the nanocrystals are well covered over the 2D N-rGO layer. Further, ɤ-Fe2O3-N-rGO nanohydrogel was applied for the catalytic reduction and electrochemical detection of ecotoxic 4-NP. A low cost, ɤ-Fe2O3-N-rGO nanohydrogel displayed an excellent catalytic activity, high recyclability (>5 cycles) and high conversion efficiency of 4-NP to 4-Aminophenol (4-AP). In addition, ɤ-Fe2O3-N-rGO nanohydrogel modified GCE displayed a wide linear sensing range (0.1-1000 µM), and a low detection limit (LOD) of 0.1 µM with excellent sensitivity, high selectivity (<1.2%) and good stability (>4 weeks). The developed sensor electrode shows the low reduction potential of -0.3 V and -0.60 V for the determination of 4-NP. The proposed ɤ-Fe2O3-N-rGO nanohydrogel is promising catalyst for the detection and removal of toxic aromatic nitro compounds in real site applications.
Assuntos
Grafite , Nitrocompostos , Técnicas Eletroquímicas , EletrodosRESUMO
Experiments using live dissociated carotid body (CB) cells for patch clamping, [Ca(++)](i) or other measurements require positive identification of the cell being recorded. At present, cell morphology is usually employed, but several cell types within the carotid body evidence similar morphologic characteristics. Therefore, we sought to develop a method utilizing a vital dye to identify glomus cells before and during experiments that require live cells, such as patch clamp studies. It was previously reported that the binding sites for peanut agglutinin (PNA) were highly expressed by all neuroendocrine-derivatives of the sympathoadrenal neural crest, including glomus cells, small, intensely fluorescent cells, PC-12 cells, and adrenal chromaffin cells in situ (katz et al. 1995). By utilizing the binding characteristics of galactose-specific lectin peanut agglutinin (PNA) on the outer cell membrane, we tested the possibility that the fluoresceinated PNA may preferentially bind to CB glomus cells. The results to date show: (1) Rhodamine tagged PNA (Rhod-PNA) binds to the live dissociated glomus cells in less than one hour incubation and can be visualized in superfused cells; (2) Rhod-PNA labeled cells are perfectly matched with tyrosine hydroxylase (TH) positive glomus cells; (3) Rhod-PNA did not interfere with Fura-2 for Ca(++) imaging; (4) Rhod-PNA bound to glomus cells in [Ca(++)](i) studies does not affect O(2) response of glomus cells. Thus fluoresceinated PNA may be a useful marker for live CB glomus studies, without adversely affecting their physiologic response.
Assuntos
Corpo Carotídeo/citologia , Corpo Carotídeo/metabolismo , Fluoresceína/metabolismo , Oxigênio/metabolismo , Aglutinina de Amendoim/metabolismo , Animais , Biomarcadores/metabolismo , Corpo Carotídeo/efeitos dos fármacos , Sobrevivência Celular , Técnicas In Vitro , Ratos , Ratos Sprague-Dawley , Coloração e RotulagemRESUMO
In mammals, transient exposure to hyperoxia for a period of weeks during perinatal life leads to impairment of the ventilatory response to acute hypoxia, which may persist long beyond the duration of the hyperoxia exposure. The impairment of the ventilatory response to hypoxia is due to hyperoxia-induced reduction of carotid chemoreceptor sensitivity to hypoxia. We previously demonstrated that hyperoxia exposure in rats, from birth to two weeks of age, profoundly reduced carotid chemoreceptor single axonal responses to acute hypoxia challenge. However, the time course and mechanisms of this impairment are not known. Therefore, we investigated the effect of hyperoxia (FiO(2) = 0.6) on neonatal rats after 1, 3, 5, 8, and 14 days of exposure, starting at postnatal day 7. Carotid chemoreceptor single unit activities, nerve conduction time and glomus cell calcium responses to acute hypoxia were recorded in vitro. After 1 day in hyperoxia, single unit spiking rate in response to acute hypoxia was increased compared to controls. After 5 days in hyperoxia, the spiking response to acute hypoxia was significantly reduced compared to controls, nerve conduction time was lengthened and the glomus cell calcium response to acute hypoxia was reduced compared to controls. We conclude that perinatal exposure to hyperoxia, in rats, impairs the glomus cell calcium response (pre-synaptic) and the afferent nerve excitability (post-synaptic). The time course indicates that hyperoxia exerts these effects within days.
Assuntos
Cálcio/metabolismo , Corpo Carotídeo/metabolismo , Corpo Carotídeo/patologia , Hiperóxia/fisiopatologia , Animais , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Espaço Intracelular/metabolismo , Condução Nervosa , Oxigênio/metabolismo , Ratos , Ratos Sprague-Dawley , Valores de Referência , Fatores de TempoRESUMO
Neuregulins (NRGs) and their receptors, the ErbB protein tyrosine kinases, are essential for neuronal development, but their functions in the adult CNS are unknown. We report that ErbB4 is enriched in the postsynaptic density (PSD) and associates with PSD-95. Heterologous expression of PSD-95 enhanced NRG activation of ErbB4 and MAP kinase. Conversely, inhibiting expression of PSD-95 in neurons attenuated NRG-mediated activation of MAP kinase. PSD-95 formed a ternary complex with two molecules of ErbB4, suggesting that PSD-95 facilitates ErbB4 dimerization. Finally, NRG suppressed induction of long-term potentiation in the hippocampal CA1 region without affecting basal synaptic transmission. Thus, NRG signaling may be synaptic and regulated by PSD-95. A role of NRG signaling in the adult CNS may be modulation of synaptic plasticity.
Assuntos
Encéfalo/fisiologia , Receptores ErbB/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Neurregulinas/fisiologia , Transdução de Sinais/fisiologia , Sinapses/fisiologia , Animais , Encéfalo/citologia , Células Cultivadas , Proteína 4 Homóloga a Disks-Large , Estimulação Elétrica , Receptores ErbB/metabolismo , Hipocampo/citologia , Hipocampo/metabolismo , Hipocampo/fisiologia , Técnicas In Vitro , Peptídeos e Proteínas de Sinalização Intracelular , Potenciação de Longa Duração/efeitos dos fármacos , Proteínas de Membrana , Proteínas do Tecido Nervoso/metabolismo , Neurregulinas/farmacologia , Neurônios/metabolismo , Ratos , Receptor ErbB-4 , Distribuição Tecidual , LevedurasRESUMO
OBJECTIVE: To study the improving effect of atorvastatin on plaque stability in diabetes mellitus (DM) mice complicated with atherosclerosis. MATERIALS AND METHODS: Apolipoprotein E (ApoE)-/- mice were used to establish the DM mouse model. Half of the mice received atorvastatin after successful modeling. ApoE-/- and C57BL/6J mice were used as controls. Oil red O staining and Masson staining were performed to detect the lipid and collagen components in mice. Immunohistochemical assay was used to observe the expressions of smooth muscle cell (SMC) and Ly-6c. The expressions of receptor for advanced glycation end products (RAGE), monocyte chemoattractant protein-1 (MCP-1) and nuclear factor-κB (NF-κB) in tissues were detected by Western blotting. Finally, the levels of serum soluble RAGE (sRAGE), advanced glycation end products (AGEs), malondialdehyde (MDA) and reduced glutathione (GSH) in mice were also detected. RESULTS: Atorvastatin reduced the area of atherosclerotic plaque and improved the stability of arterial plaque through reducing lipid deposition, the number of macrophages and SMC, increasing collagen fibers. In mice in atorvastatin group, the levels of serum AGEs and sRAGE were decreased. Moreover, atorvastatin inhibited the downstream pathway of RAGE as well as DM, thus inducing the oxidative stress. CONCLUSIONS: Atorvastatin improves plaque stability in diabetic atherosclerosis through the RAGE pathway.
Assuntos
Aterosclerose/sangue , Atorvastatina/uso terapêutico , Diabetes Mellitus/sangue , Placa Aterosclerótica/sangue , Receptor para Produtos Finais de Glicação Avançada/sangue , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Atorvastatina/farmacologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/patologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/patologiaRESUMO
This corrects the article DOI: 10.1038/cddis.2014.82.
RESUMO
An electrochemical sensor is built using vertically grown multi-walled carbon nanotubes (MWNTs) micro-array to detect methanol concentration in water. This study is done for the potential use of the array as methanol sensor for portable units of direct methanol fuel cells (DMFCs). Platinum (Pt) nanoparticles electro-deposited CNTs (Pt/CNTs) electrode shows high sensitivity in the measurement of methanol concentration in water with cyclic voltammetry (CV) measurement at room temperature. Further investigation has also been undertaken to measure the concentration by changing the amount of the mixture of methanol and formic acid in water. We compared the performance of our micro array sensor built with Pt/CNTs electrodes versus that of Pt wire electrode using CV measurement. We found that our Pt/CNTs array sensor shows high sensitivity and detects methanol concentrations in the range of 0.04 M to 0.10 M. In addition, we found that co-use of formic acid as electrolyte enables us to measure up to 1.0 M methanol concentration.
Assuntos
Eletroquímica/métodos , Nanotecnologia/métodos , Nanotubos de Carbono/química , Relação Dose-Resposta a Droga , Fontes de Energia Elétrica , Eletrodos , Formiatos/química , Nanopartículas Metálicas/química , Metanol/química , Microeletrodos , Microscopia Eletrônica de Varredura , Nanopartículas/química , Platina/química , Propriedades de SuperfícieRESUMO
The only ras oncogene as yet identified in cells from human fibrosarcomas is N-ras, but the relationship between N-ras oncogene expression and the malignant state of these cell lines is not known. To determine if expression of an N-ras oncogene causes human cells to become malignant, we transfected the N-ras oncogene from human leukemia cell line 8402, cloned into a high expression vector pSV N-ras, into MSU-1.1 cells, a nontumorigenic, infinite life span fibroblast cell strain with a normal morphology and a stable near-diploid karyotype. The transformants formed distinct foci composed of morphologically transformed cells. Cells from such foci expressed higher than normal levels of N-ras protein, exhibited growth factor independence, and formed large colonies in soft agar at a high frequency. Injection of progeny of these focus-derived cells s.c. into athymic mice resulted in progressively growing, invasive malignant tumors (round cell, spindle cell, or giant cell sarcomas) which reached a diameter of 6 mm in 3 to 4 weeks. Injection of focus-derived or tumor-derived cells i.v. resulted in tumors in various organs of the mice. The focus-derived cell strain tested, as well as the majority of the cells derived from the tumor it produced, exhibited the same near-diploid karyotype as the parental MSU-1.1 cells. Cells transfected with an N-ras oncogene that was expressed at a normal level formed only a single, indistinct focus, and cells from that focus were not malignant.
Assuntos
Transformação Celular Neoplásica , Genes ras , Transfecção , Animais , Adesão Celular , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Bandeamento Cromossômico , Meios de Cultura , DNA de Neoplasias/genética , DNA de Neoplasias/isolamento & purificação , Substâncias de Crescimento/farmacologia , Humanos , Cariotipagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Hibridização de Ácido Nucleico , Plasmídeos , Mapeamento por RestriçãoRESUMO
Objective: To understand the genetic and molecular epidemiologic characteristics of 63 strains of Japanese encephalitis virus (JEV) isolated in Yunnan province, China during 1977-2010. Methods: Suckling mice were inoculated with viruses continuously and the viral nucleic acid were extracted from the brain-grinding supernatants of the infected and moribund mice, then the gene fragments of E region were amplified by RT-PCR. Bioinformatics (Clustal X, DNAstar, Mega 5.0 and other software) was used to analyze the nucleotide and deduced amino acid sequences and phylogenetic trees. Results: Yunnan strains of JEV could cause illness and deaths in suckling mice. The results of virus nucleic acid detection and sequencing indicated that nucleotide sequences of E gene of the 63 virus strains were obtained. Phylogenetic tree and homology analyses based on E genomes showed that 47 strains of the experimental virus belonged to genotype 1 (G-1) and 16 strains belonged to genotype 3 (G-3). The 47 isolates of G-1 were divided into 2 clades, of them, the earliest isolates of G-1 (M28, 1977 and BN82215, 1982) in Yunnan of China and the early isolates of G-1 (U70416, 1982; DQ084229, the year is unknown) in Thailand were in one clade, and the isolates of G-1 from 2007-2010 in Yunnan could be divided into 2 subgroups. The 16 isolates of G-3 from Yunnan were divided into 3 clades, among them, the isolates from 1970-1990s in Yunnan were in two clades, and the isolates from 2004 in Yunnan were in one clade. In addition, their main amino acid sites of antigenicity, pathogenic, virulence of both G-1 and G-3 had no significant change. Conclusion: JEV G-1 and G-3 co-circulated in Yunnan, and G-1 was predominant. The JEV strains isolated in different years and areas in Yunnan had different molecular epidemiologic characteristics and genetic diversity. The results of this study suggested that JEV G-1 might originate from Yunnan of China and adjacent Southeast Asia region.
Assuntos
Vírus da Encefalite Japonesa (Subgrupo) , Encefalite Japonesa , Sequência de Aminoácidos , Animais , Sequência de Bases , Encéfalo , China , Biologia Computacional , Vírus da Encefalite Japonesa (Espécie) , Genótipo , Humanos , Camundongos , Epidemiologia Molecular , Filogenia , VirulênciaRESUMO
Ketamine and phencyclidine are structurally similar compounds that share many pharmacological actions, some of which are similar to the phenethylamines amphetamine and cathione. In order to integrate structural features of ketamine and cathinone, two groups of analogues, which are more conformationally restricted compared to the parent compounds, were synthesized for biological evaluation. These included 1-amino-1-methyl-2-tetralone and 2-amino-2-methyl-1-tetralone was well as several N-substituted derivatives of these molecules. Locomotor activity testing in mice revealed that 2-amino-2-methyl-1-tetralone caused an increase in locomotor activity while 1-amino-1-methyl-2-tetralone depressed spontaneous locomotor activity. None of the compounds produced hypnosis or profound ataxia.
Assuntos
Ketamina/análogos & derivados , Atividade Motora/efeitos dos fármacos , Tetralonas , Alcaloides , Animais , Fenômenos Químicos , Química , Hipnóticos e Sedativos , Masculino , Camundongos , Tetra-Hidronaftalenos/síntese química , Tetra-Hidronaftalenos/farmacologiaRESUMO
UNLABELLED: Paclitaxel, an antineoplastic agent that stabilizes microtubules and arrests cells in the G2/M cell cycle phase, has shown activity against many common cancers, including ovarian and breast tumors. In order to evaluate the potential value of radiolabeled paclitaxel as an imaging tool in tumors, we synthesized 111In-DEPA-paclitaxel and investigated its biodistribution and gamma scintigraphic imaging properties. METHODS: Mice bearing a paclitaxel-responsive mammary tumor (MCA-4) were used. DTPA-paclitaxel was labeled with 111In with a radiochemical yield of 84% and radiochemical purity of 90%. Each mouse received 5 microCi of radiotracers intravenously for biodistribution studies and 100 microCi for gamma scintigraphic studies. Indium-111-DTPA was used as a control. RESULTS: In tumor-bearing mice, 111In-DTPA was characterized by rapid clearance from the plasma with negligible retention in the tumor, the liver and other body parts. In contrast, 111In-DTPA-paclitaxel exhibited a pharmacological profile resembling that of paclitaxel. Furthermore, a significant uptake of 111In-DTPA-paclitaxel was observed in the tumor. The tumor-to-muscle ratios were 2.64, 3.16 and 6.94 at 30 min, 2 hr and 24 hr, respectively, although absolute uptake in the tumor decreased from 1.95% (injected dose/g) at 30 min to 0.21% at 24 hr after injection. The tumor-to-blood ratio reached 50 at 24 hr after injection. Gamma scintigraphy and autoradiographic studies clearly showed the retention of radiolabeled paclitaxel in the tumor 24 hr after injection. CONCLUSION: These studies suggest that 111In-DTPA-paclitaxel may be clinically useful in studying the uptake of paclitaxel in solid tumors.
Assuntos
Antineoplásicos Fitogênicos/farmacocinética , Radioisótopos de Índio , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/metabolismo , Paclitaxel/farmacocinética , Ácido Pentético , Animais , Antineoplásicos Fitogênicos/síntese química , Autorradiografia , Quelantes/síntese química , Quelantes/farmacocinética , Feminino , Radioisótopos de Índio/farmacocinética , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos , Paclitaxel/síntese química , Ácido Pentético/síntese química , Ácido Pentético/farmacocinética , Cintilografia , Distribuição TecidualRESUMO
UNLABELLED: We investigated the diagnostic accuracy of FDG-PET in the detection of recurrent lung cancer. METHODS: Thirty-nine lesions in 38 patients with clinically suspected recurrent or residual lung cancer were studied with PET. All PET images were visually interpreted in conjunction with thoracic CT or MRI. Semiquantitative analysis using standardized uptake values (SUVs) was also performed in 25 lesions. FDG-PET diagnoses were correlated with pathological diagnoses and clinical outcome. RESULTS: The sensitivity and specificity of FDG-PET for detecting recurrent tumors were 100% (26/26) and 61.5% (8/13), respectively. The difference in mean SUV between recurrent tumors and noncancerous lesions was statistically significant [11.2 +/- 5.7 (n = 16) vs. 3.5 +/- 1.8 (n = 9), p < 0.0001]. False-positive results showed relatively lower SUVs than true-positives and also demonstrated increased uptake in a curvilinear rather than nodular shape. CONCLUSION: FDG-PET is useful for detecting recurrent lung cancer after treatment. False-positive diagnoses might be reduced by analysis of uptake shape and serial changes in SUV, but further study is needed.