Technetium-99m labelled liposomes to image experimental arthritis

OBJECTIVES—Liposomes sterically stabilised with polyethylene glycol (PEG) labelled with technetium-99m were tested for their ability to image adjuvant arthritis in a rat model.
METHODS—Adjuvant arthritis was induced in the ankle joint of the left hind foot by injection of Mycobacterium butyricum in Freund's incomplete adjuvant in the foot pad. Seven days later animals received the following radiopharmaceuticals labelled with ^99mTc (a) non-PEG-liposomes, (b) PEG-liposomes or (c) non-specific human polyclonal IgG. For each of the radiopharmaceuticals the in vivo distribution of the radiolabel was monitored both scintigraphically as well as by counting the dissected tissues at two, eight, and 24 hours after injection.
RESULTS—The pharmacokinetics of the radiopharmaceuticals differed considerably (half life in the blood: PEG-liposomes (18 hours) > ^99mTc-IgG (3 hours) > non-PEG liposomes (1 hour)). The inflamed focus was visualised with each of the agents. The uptake of each of the radiopharmaceuticals in the inflamed ankle region correlated with their residence time in the blood (inflamed joint uptake: PEG liposomes (1.15% injected dose (ID)/g)>^99mTc-IgG (0.35% ID/g)>non-PEG-liposomes (0.05% ID/g)). Quantitative analysis of the images showed that the inflamed ankle to background ratio was highest with the PEG-liposomes (7.5 at 24 hours after injection), while with the other two agents this ratio did not exceed 4.
CONCLUSION—This study shows that ^99mTc-labelled PEG-liposomes may be an excellent agent to visualise arthritis. Increased label uptake in the inflamed joint and increased target to background ratios can be obtained with PEG-liposomes because of their long circulating properties. In addition to their use as vehicles for scintigraphic imaging of arthritis PEG-liposomes might also be used for the site specific delivery of antirheumatic drugs.

     

Intravenous fate of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes

The objective of this study was to assess the in vivo fate of poly(2-(dimethylamino)ethyl methacrylate) (pDMAEMA)-based polyplexes after intravenous administration into mice. Circulation kinetics and tissue distribution in terms of plasmid localization and transfection efficiency were assessed. To gain more insight into the observed biodistribution and gene expression profile, the interaction of pDMAEMA-based polyplexes with blood components (erythrocytes and albumin) was investigated in vitro. In the case of i.v. injection of positively charged polyplexes at a dose of 30 microg DNA most of the radioactivity was found in the lungs and the liver 60 min after injection. In the case of pDMAEMA/DNA polyplexes with a negative charge, uptake occurred mainly by the liver. Administration of positively charged complexes at a 30 microg DNA dose resulted in reporter gene expression primarily in the lungs. Injection of negatively charged complexes and naked plasmid did not result in luciferase expression in any of the organs examined. In vitro turbidity experiments showed the induction of a charge dependent aggregation process upon addition of albumin to the polyplexes pointing out to the involvement of aggregate formation in the dominant lung uptake of the positively charged polyplexes. Also, incubations of polyplexes after pre-incubation with a physiological concentration of albumin with washed erythrocytes confirmed that polyplexes induce the formation of extremely large structures. This paper underlines the need for the design of systems with reduced interaction with blood components to promote the delivery of DNA to target tissues outside the lungs.     

创伤后迟发性脑肿胀的临床特点与治疗

目的 探讨创伤后迟发性脑肿胀的临床特点、发病机制与治疗。方法 回顾性分析1998年1月～2005年6月年收治的17例迟发性脑肿胀患者的临床特点和救治情况。结果 所有颅脑损伤患者采用保守治疗后均有好转，但于伤后5-10d出现恶化，CT复查有脑肿胀，经加强综合脱水等治疗后16例治愈，1例死亡。结论 迟发性脑肿胀好发于对冲性额、颞叶挫裂伤伴明显蛛网膜下腔出血、硬膜下薄层血肿及早期CT有脑肿胀者。其发病机制可能与创伤后的迟发性脑血管痉挛、微循环障碍、静脉回流障碍及甘露醇作用下降等因素有关。此类患者病情隐蔽性强，应加强观察、积极行CT复查，如能早期明确诊断，保守治疗多数效果良好。     

Comparison of novel computer detectors and human performance for spike detection in intracranial EEG.

OBJECTIVE: Interictal spikes in intracranial EEG (iEEG) may correlate with epileptogenic cortex, but review of interictal iEEG is labor intensive. Accurate automated spike detectors are necessary for understanding the role of spikes in epileptogenesis. METHODS: The sensitivity, accuracy and reproducibility of three automated iEEG spike detectors were compared against two human EEG readers using iEEG segments from eight patients. A consensus set of detections was generated for detector calibration. Spike verification was calculated after both human EEG readers independently reviewed all detections. RESULTS: Humans and two of the three automated detectors demonstrated comparable accuracy. In four patients, automated spike detection sensitivity was >70% and accuracy was >50%. In the remaining four patients, EEG background morphology resulted in poorer performance. Blinded human verification accuracy was 76.7+/-6.6% for computer-detected spikes, and 84.5+/-4.1% for human-detected spikes. CONCLUSIONS: Automated iEEG spike detectors perform comparably to humans, but sensitivity and accuracy are patient dependent. Humans verified the majority of computer-detected spikes. SIGNIFICANCE: In some patients automated detectors may be used for mapping spike occurrences in epileptic networks. This may reveal associations between spike distribution, seizure onset, and pathology.     

Retrorenal colon: implications for percutaneous diskectomy

It has been recommended that computed tomography (CT) with the patient prone be performed in every patient undergoing percutaneous diskectomy; this would enable detection of a retrorenal location of the colon, which could interfere with the percutaneous procedure. In this evaluation of 346 prone CT studies, only one patient (0.29%) was found to have retrorenal or retropsoas bowel that would have been perforated at diskectomy. Because of this extremely low prevalence, the performance of prone CT in every patient undergoing percutaneous lumbar diskectomy is not believed to be necessary.     

肾移植受者血清巨细胞病毒IgE和IgA抗体检测

采用间接ＥＬＩＳＡ检测２３名肾移植受者血清巨细胞病毒（ＣＭＶ）抗体，共检出１８名（７８％）活动性ＣＭＶ感染，其中１０名（４４％）为原发性感染。结果证实ＣＭＶ－ＩｇＥ和－ＩｇＡ具有较好的血清学诊断价值，优于ＣＭＶ－ＩｇＭ。     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.