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Turkman N Shavrin A Paolillo V Yeh HH Flores L Soghomonian S Rabinovich B Volgin A Gelovani J Alauddin M 《Nuclear medicine and biology》2012,39(4):593-600
IntroductionThe cannabinoid receptor type 2 (CB2) is an important target for development of drugs and imaging agents for diseases, such as neuroinflammation, neurodegeneration and cancer. Recently, we reported synthesis and results of in vitro receptor binding of a focused library of fluorinated 2-oxoquinoline derivatives as CB2 receptor ligands. Some of the compounds demonstrated to be good CB2-specific ligands with Ki values in the nanomolar to subnanomolar concentrations; therefore, we pursued the development of their 18F-labeled analogues that should be useful for positron emission tomography (PET) imaging of CB2 receptor expression. Here, we report the radiosynthesis of two 18F-labeled 2-oxoquinoline derivatives and the preliminary in vitro and ex vivo evaluation of one compound as a CB2-specific radioligand.Methods4-[18F]fluorobenzyl amine [18F]-3 was prepared by radiofluorination of 4-cyano-N,N,N-trimethylanilinium triflate salt followed by reduction with LiAlH4 and then coupled with acid chlorides 11 and 12 to afford [18F]-13 and [18F]-14. In vitro CB2 receptor binding assay was performed using U87 cells transduced with CB2 and CB1 receptor. Ex vivo autoradiography was performed with [18F]-14 on spleen and on CB2- and CB1-expressing and wild-type U87 subcutaneous tumors grown in mice.ResultsThe radiochemical yields of [18F]-13 and [18F]-14 were 10%–15.0% with an average of 12% (n=10); radiochemical purity was >99% with specific activity 1200 mCi/μmol. The dissociation constant Kd for [18F]-14 was 3.4 nM. Ex vivo autoradiography showed accumulation of [18F]-14 in the CB2-expressing tumor.ConclusionTwo new [18F]-labeled CB2 ligands have been synthesized. Compound [18F]-14 appears to be a potential PET imaging agent for the assessment of CB2 receptor expression; however, poor solubility restrain its use in vivo. 相似文献
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F Aydin† N Senturk† L Yildiz† MT Canturk† AY Turanli† 《Journal of the European Academy of Dermatology and Venereology》2004,18(6):716-717
Neutrophilic dermatosis of the dorsal hands is a recently described disorder, which is similar to Sweet's syndrome. It is characterized by erythematous plaques, pustules and haemorrhagic bullae located solely on the dorsal surface of the hands. We describe a 57-year-old man with neutrophilic dermatosis of the dorsal hands that occurred following exposure to a chemical fertilizer. There are few cases reported in the literature regarding neutrophilic dermatosis and the aetiology remains unclear. For the present case, we propose that neutrophilic dermatosis of the dorsal hands might have been induced by the chemical fertilizer. 相似文献
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Safety and immunogenicity of the novel seasonal preservative‐ and adjuvant‐free influenza vaccine: Blind,randomized, and placebo‐controlled trial
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Gulbanu Sarsenbayeva Yevgeniy Volgin Markhabat Kassenov Timur Issagulov Nikolay Bogdanov Abylay Sansyzbay Ruslan Abitay Ainur Nurpeisova Altynay Sagymbay Zhumagali Koshemetov Marina Stukova Zhanna Buzitskaya Ilyas Кulmagambetov Dinara Karabayeva Timur Davlyatshin Berik Khairullin 《Journal of medical virology》2018,90(1):41-49
The producers of influenza vaccines are not capable today to meet the global demand for an influenza vaccine in case of pandemic, so the World Health Organization recommends to develop the own influenza vaccine production in each country. A domestic preservative‐ and adjuvant‐free trivalent split vaccine against seasonal influenza was developed at the Research Institute for Biological Safety Problems. The paper presents the results of assessing safety and immunogenicity of the influenza split vaccine after single immunization of healthy volunteers aged 18‐50 years in the course of Phase I Clinical Trials. This study was randomized, blind, and placebo‐controlled. The volunteers were intramuscularly vaccinated with a dose of split vaccine or placebo. The study has shown that all local and systemic reactions had low degree of manifestation and short‐term character, so there was no need in medication. Serious side effects were not observed. On day 21 post vaccination the portion of vaccinated persons with fourfold seroconversions to influenza А/H1N1pdm09 virus was 100.0%, to influenza А/H3N2 virus—95.5%, to influenza B virus—81.8%, and in placebo group this index was 0%. Seroprotection rates against influenza А/H1N1pdm09, А/H3N2 and B viruses were 95.5, 86.3, and 72.7%, respectively. Geometric mean titers (GMT) of antibodies by day 21 post vaccination reached 175.7 for influenza А/H1N1pdm09 virus, 64.2 for influenza А/H3N2 virus, and 37.6 for influenza B virus; in placebo group GMT growth was not observed. So, the seasonal influenza split vaccine is well tolerated and fits all immunogenicity criteria for human influenza vaccines. 相似文献
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目的:研制并测试喉切除术后患者生存质量量表。方法:依据1993年WHO制定的生存质量一般准则,通过指标的收集和筛选,制定喉切除术后患者生存质量量表。选择1996-06/2002-06在中山大学附属第一医院因喉癌行喉切除术后满6个月的患者81例,对36例喉部分切除和45例喉全切除的患者进行上述量表问卷调查,考核该量表的可行性、信度和效度。结果:①量表指标筛选结果:经过对收集的81个指标的多次筛选,最终得到生存质量量表的22个评价指标。②量表结构:由22个评价指标及1个有关患者对自己总体健康状况和生存质量评价的问题(满分100分)组成。覆盖了身体机能、喉功能、心理状态、独立生活能力、社会关系与环境以及气管造口等6个方面。采用等级描述评分法,每个问题有5个选项,由差到好依次分值为1~5分。③量表的接受率和完成率分别为73%和93%,完成时间为10min以内;分半信度、克朗巴赫系数和方差比分别为0.842,0.889和0.155,表明量表有较好的信度。通过测试准则关联效度及内容效度,表明量表是有效的。结论:设计的喉切除术后患者生存质量量表有喉切除术的专业特性,具有较好的可行性、信度及效度。 相似文献
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Consequences of prenatal alcohol exposure (AE) include motor hyperactivity, disrupted sleep and cognitive deficits. Hypothalamic orexin (ORX)-synthesizing neurons are important for the maintenance of vigilance and regulation of motor activity but their hyperactivity may contribute to anxiety disorders. Using a rat model, we tested whether ORX plays a role in behavioral consequences of prenatal AE. Male rat pups received 2.625 g/kg of alcohol (AE group) intragastrically twice daily on postnatal days (PD)4-9, a developmental period equivalent to the third trimester of human pregnancy. Control pups were sham-intubated (S group). On PD12-14, they received daily injections of either the ORX-1 receptor antagonist, SB-334867 (SB; 20 mg/kg, i.p.) or vehicle (V) during the lights-off period. On PD16, they were subjected to the homing response (HR) test. On PD17, their motor activity was monitored in a novel environment. The percentage of tests in which HR acquisition was not achieved and the number of trials needed to reach the shortest HR latency were higher, whereas the percentage of successful trials was lower, in AE-V than in S-V rats (p = 0.0009-0.03). In contrast, these measures were not significantly different between AE-SB and either S-SB or S-V rats. Motor activity in AE-V rats was significantly higher than in S-V (p = 0.003), S-SB (p = 0.007) or AE-SB (p = 0.02) rats, with no difference between S-SB and AE-SB group. Our findings suggest that excessive activity of ORX neurons contributes to motor hyperactivity and impaired HR acquisition following perinatal AE and that these symptoms may be alleviated by systemic antagonism of ORX-1 receptors. 相似文献
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J. THALER C. AY N. MACKMAN R. M. BERTINA A. KAIDER C. MAROSI N. S. KEY D. A. BARCEL W. SCHEITHAUER G. KORNEK C. ZIELINSKI I. PABINGER 《Journal of thrombosis and haemostasis》2012,10(7):1363-1370
Summary. Background: Tissue factor (TF) expression by tumors contributes to tumor growth. Release of TF‐positive microparticles (MPs) may contribute to venous thromboembolism (VTE). Objectives: To conduct a prospective cohort study to determine whether elevated MP‐associated TF (MP‐TF) activity is predictive of VTE and mortality in four cancer types. Patients/Methods: We determined MP‐TF activity in pancreatic, gastric, colorectal and brain cancer patients. We used a chromogenic endpoint assay for all patients and also a chromogenic kinetic assay for patients with pancreatic and brain cancer. Results: During follow‐up, 12/60 (20%) pancreatic, 6/43 (14%) gastric, 12/126 (10%) colorectal and 19/119 (16%) brain cancer patients developed VTE; 46/60 (77%), 30/43 (70%), 47/126 (37%) and 67/119 (56%), respectively, died. MP‐TF activity levels were highest in pancreatic cancer. We did not find a statistically significant association of MP‐TF activity with the risk of VTE in any of the four cancer types by using two statistical methods. An association of MP‐TF activity with the risk of mortality was detected in pancreatic cancer with the endpoint assay (hazard ratio [HR] 1.8 and 95% confidence interval [CI] 1.4–2.3 per doubling of activity, P < 0.001) and the kinetic assay (HR 1.2, 95% CI 1.1–1.4, P < 0.001); adjustment for type of treatment was not performed. In pancreatic cancer, MP‐TF activity correlated with D‐dimer level (endpoint assay, r = 0.51; chromogenic assay, r = 0.48), and a correlation between assays (r = 0.61) was found. Conclusion: MP‐TF activity was not associated with future VTE in pancreatic, gastric, colorectal and brain cancer. However, we found a strong association of MP‐TF activity with mortality in pancreatic cancer. MP‐TF activity might be reflective of an aggressive pancreatic cancer phenotype. 相似文献
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