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1.
Yubin Miao Said D Figueroa Darrell R Fisher Herbert A Moore Richard F Testa Timothy J Hoffman Thomas P Quinn 《Journal of nuclear medicine》2008,49(5):823-829
Peptide-targeted alpha-therapy with 7.4 MBq of (212)Pb-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-ReO-[Cys(3,4,10),d-Phe(7),Arg(11)]alpha-MSH(3-13) ((212)Pb-DOTA-Re(Arg(11))CCMSH) cured 45% of B16/F1 murine melanoma-bearing C57 mice in a 120-d study, highlighting its melanoma treatment potential. However, there is a need to develop an imaging surrogate for patient-specific dosimetry and to monitor the tumor response to (212)Pb-DOTA-Re(Arg(11))CCMSH therapy. The purpose of this study was to evaluate the potential of (203)Pb-DOTA-Re(Arg(11))CCMSH as a matched-pair SPECT agent for (212)Pb-DOTA-Re(Arg(11))CCMSH. METHODS: DOTA-Re(Arg(11))CCMSH was labeled with (203)Pb in 0.5 M NH(4)OAc buffer at pH 5.4. The internalization and efflux of (203)Pb-DOTA-Re(Arg(11))CCMSH were determined in B16/F1 melanoma cells. The pharmacokinetics of (203)Pb-DOTA-Re(Arg(11))CCMSH was examined in B16/F1 melanoma-bearing C57 mice. A micro-SPECT/CT study was performed with (203)Pb-DOTA-Re(Arg(11))CCMSH in a B16/F1 melanoma-bearing C57 mouse at 2 h after injection. RESULTS: (203)Pb-DOTA-Re(Arg(11))CCMSH was easily prepared in NH(4)OAc buffer and completely separated from the excess nonradiolabeled peptide by reversed-phase high-performance liquid chromatography (RP-HPLC). (203)Pb-DOTA-Re(Arg(11))CCMSH displayed fast internalization and extended retention in B16/F1 cells. Approximately 73% of (203)Pb-DOTA-Re(Arg(11))CCMSH activity internalized after a 20-min incubation at 25 degrees C. After incubation of the cells in culture medium for 20 min, 78% of internalized activity remained in the cells. (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited a biodistribution pattern similar to that of (212)Pb-DOTA-Re(Arg(11))CCMSH in B16/F1 melanoma-bearing mice. (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited a peak tumor uptake of 12.00+/-3.20 percentage injected dose per gram (%ID/g) at 1 h after injection. The tumor uptake gradually decreased to 3.43+/-1.12 %ID/g at 48 h after injection. (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited a peak tumor-to-kidney uptake ratio of 1.53 at 2 h after injection. The absorbed doses to the tumor and kidneys were 4.32 and 4.35 Gy, respectively, per 37 MBq. Whole-body clearance of (203)Pb-DOTA-Re(Arg(11))CCMSH was fast, with approximately 89% of the injected activity cleared through the urinary system by 2 h after injection. (203)Pb showed 1.6-mm SPECT resolution, which was comparable to (99m)Tc. Melanoma lesions were visualized through SPECT/CT images of (203)Pb-DOTA-Re(Arg(11))CCMSH at 2 h after injection. CONCLUSION: (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited favorable pharmacokinetic and tumor imaging properties, highlighting its potential as a matched-pair SPECT agent for (212)Pb-DOTA-Re(Arg(11))CCMSH melanoma treatment. 相似文献
2.
Abstract: Juvenile xanthogranuloma is a benign histiocytic skin disorder encountered primarily in infancy and childhood. Approximately 0.4% of cases exhibit ocular manifestations, which can result in glaucoma and blindness. We present a case of a 7-month-old male with unilateral glaucoma associated with Juvenile xanthogranuloma, and emphasize the importance of an ocular screening in patients with Juvenile xanthogranuloma, especially those with periocular lesions. 相似文献
3.
Yulu Miao Mingxia Zhang Yulin Nie Wan Zhao Bin Huang Zhengming Jiang Shaoxiong Yu Zhibin Huang Hongjin Fu 《中国神经再生研究》2007,2(2):126-128
BACKGROUND: Besides local changes of cranial parenchymal cells, hemorrhage, etc., severe traumatic brain injuries also cause the changes of total body fluid and various functions, and the changes of lymphocytes and T lymphocyte subsets should be paid more attention to. OBJECTIVE: To reveal the changing laws of T lymphocyte subsets after severe traumatic brain injury, and compare with mild to moderate brain injury. DESIGN: A comparative observation. SETTINGS: Department of Neurosurgery, Longgang District Buji People's Hospital of Shenzhen City; Central Laboratory of Shenzhen Hospital of Prevention and Cure for Chronic Disease. PARTICIPANTS: All the subjects were selected from the Department of Neurosurgery, Longgang District Buji People's Hospital of Shenzhen City from August 2002 to August 2005. Thirty patients with severe brain injury, whose Glasgow coma score (GCS) was ≤ 8 points, were taken as the experimental group, including 21 males and 9 females, aging 16 - 62 years. Meanwhile, 30 patients with mild traumatic brain injury were taken as the control group (GCS ranged 14- 15 points), including 18 males and 12 females, aging 15 -58 years. All the subjects were in admission at 6 hours after injury, without disease of major organs before injury Informed consents were obtained from all the patients or their relatives. METHODS: (1) The T lymphocytes and the subsets in peripheral blood were detected with immunofluorescent tricolor flow cytometry at l, 3, 7 and 14 days after injury in both groups. (2) The conditions of pulmonary infections were observed at 4 days after injury. The differences of measurement data were compared with the t test. MAIN OUTCOME MEASURES: Changes of T lymphocytes subsets at 1 - 14 days after severe and mild or moderate traumatic injury. RESULTS: Finally, 28 and 25 patients with mild to moderate traumatic brain injury, whereas 25 and 21 patients with severe traumatic brain injury were analyzed at 7 and 14 days respectively, and the missed ones died due to the development of disease. (1) Changes of T lymphocyte subsets: At 1 and 3 days after injury, CD3, CD4, CD8, CD4/CD8 began to decrease, whereas CD8 increased in the experimental group, which were very significantly different from those in the control group (t =2.77 - 3.26, P 〈 0.01), and began to recover at 7 days, which were significantly different from those in the control group (t = 2.06 - 2.24, P 〈 0.05), and generally recovered to the normal levels at 14 days (P 〉 0.05). (2) Conditions of pulmonary infections: At 4 days after injury, the rate of pulmonary infection was significantly different between the experimental group and control group [73% (22/30), 0, x2=37.29, P 〈 0.01]. CONCLUSION: Patients with severe traumatic brain injury suffer from damages of cellular immune function at early period (within 7 days), and they are easily to be accompanied by pulmonary infections. 相似文献
4.
Ziprasidone (Geodone), a novel atypical antipsychotic agent, is recently approved for the treatment of schizophrenia. It undergoes extensive metabolism in preclinical species and humans after oral administration, and only a very small amount of administered dose is excreted as unchanged drug. In vitro studies using human liver microsomes have shown that the oxidative metabolism of ziprasidone is mediated primarily by CYP3A4. However, coadministration of ziprasidone with ketoconazole, a CYP3A4 inhibitor, showed only a modest increase in its exposure. Therefore, in vitro metabolism of ziprasidone was investigated in hepatic cytosolic fractions to further understand its clearance mechanisms in preclinical species and humans. The major metabolite from incubation of ziprasidone in cytosolic fractions of rat, dog, and human was characterized by liquid chromatography-tandem mass spectrometry and found to be the product of reductive cleavage. Derivatization and hydrogen/deuterium exchange were used to deduce that the addition of two hydrogen atoms had occurred at the benzisothiazole moiety. Further studies to determine the enzyme involved in the formation of this metabolite are currently in progress. The identification of this novel metabolite in cytosol has clarified the clearance mechanism of ziprasidone in humans and preclinical species. 相似文献
5.
赛赓啶对 KBV200细胞多药抗性的逆转作用 总被引:3,自引:0,他引:3
研究赛赓啶对KBV200细胞多药抗性的逆转作用及逆转机制。在KBV200细胞,采用MTT法,测出赛赓啶对长春新碱、阿霉素和鬼臼乙叉甙耐药的逆转系数分别为5.5,2.0和1.9,而对5-氟尿嘧啶、美法仑的细胞毒性作用无明显影响,表明赛赓啶为多药抗性逆转剂。荧光分光光度法测定表明,赛赓啶可使KBV200细胞内阿霉素蓄积量增加。流式细胞荧光测定显示赛赓啶可增加罗丹明123的蓄积并减慢其外排。免疫细胞化学及狭缝杂交表明赛赓啶不影响KBV200细胞的P-糖蛋白染色深度和 mdr1 RNA 表达水平。以上结果提示赛赓啶的多药抗性逆转机制是抑制P-糖蛋白泵的功能。 相似文献
6.
为选择中等场强的MRI听神经瘤成像最佳序列。收集手术和病理证实的听神经瘤135例,分析序列Ⅰ、Ⅱ对内听道中心层面、三叉神经显示率及MR征象的显示情况。结果:序列I择内听道中心层面及三叉神经的显示均优于序列Ⅱ,序列Ⅱ在显示肿瘤内囊变、出血、不肿优于序列I;对肿瘤钙化、肿瘤血管、脑干移位的观察,两者相仿。结果显示:序列I在中等场经下作为听神经瘤成像的首选序列,并中运用到小脑角区MRI成像。 相似文献
7.
8.
雷公藤生物碱的分离鉴定 总被引:8,自引:0,他引:8
我们从雷公藤(TripterygiumWilfordiiHook.f.)中按常法分离得到总碱后经HPLC分析出现8个峰,经硅胶柱层析及硅胶RP-18反相中压柱层析分离得到5个生物碱,由化学方法和光谱分析证明为雷公藤吉碱(Wilforgine20).雷公藤次碱(Wilforine21),雷公藤春碱(Wilfortrine22),雷公藤碱戊(Wilforidine23),呋喃南蛇碱(Celafurine16)。HPLC分析指出含量最高为雷公藤吉碱,其次为呋喃南蛇碱。 相似文献
9.
Monoclonal antibodies were raised against a specific human sperm protein and designated as the YWK-II mAb. The partial cDNA encoding the protein was isolated from a rat testis lambda gt11 expression library and the amino acid sequence of the protein was deduced. The cytoplasmic-transmembrane domains of the deduced protein had high homology with the A4 amyloid precursor protein of Alzheimer's disease. To evaluate the stage of spermatogenesis when the gene was expressed, single-stranded 35S-labeled RNA probes were prepared from the cDNA. By an in situ hybridization technique the mRNA for the antigen was detected in germ cells at all stages of spermatogenesis. The finding that the gene is expressed in spermatogonia suggests possible involvement in the initiation of germ cell differentiation or in the detachment of spermatogonia from the basement membrane. 相似文献
10.
豚鼠中耳(听泡)内滴入0.5%、1%、2%环丙沙星与庆大霉素滴耳液7天或21天,借助光镜和扫描电镜观察内耳的显微和超微结构变化。结果证明环丙沙星对内耳没有明显的毒性作用。庆大霉素则使耳蜗明显受损,以底回为重,Corti’s器外毛细胞坏死较多,内毛细胞及支持细胞病变较轻。位觉斑耳石脱落,毛细胞纤毛粘连、脱落。壶腹嵴中央区纤毛也缺失。本实验对客观评价环丙沙星对内耳的作用及临床使用提供了形态学资料。 相似文献