Poly(ortho ester) nanoparticles targeted for chronic intraocular diseases: ocular safety and localization after intravitreal injection

Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5?mg/ml and 10?mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases.     

Melatonin Receptors on Ovine Pars Tuberalis: Characterization and Autoradiographicai Localization

The functional significance of the pars tuberalis (PT) of the mammalian adenohypophysis has remained an enigma (1, 2). One view of its function is that it acts as an auxiliary gland to support the endocrine role of the pars distalis (PD) (2), as it has been shown to contain immunocytochemically identifiable thyrotrophs and gonadotrophs (1). Many of the cells of the PT are, however, ultrastructurally unique suggesting an independent function for this tissue. Our recent demonstration that the PT of the rat is a major binding site for the ligand iodomelatonin lends further support to this idea (3). We have utilized the highly specific ligand [¹²⁵l]melatonin, and have demonstrated that it binds exclusively, with very high affinity, to the PT but not the PD of the adult sheep adenohypophysis. These findings support the conclusion that the PT has a distinct role in relation to melatonin action and seasonal reproduction.     

应用卵圆孔定位仪治疗三叉神经痛

目的总结卵圆孔定位仪在选择性经皮温控射频热凝治疗三叉神经痛的应用方法和技巧。方法对三叉神经第Ⅱ、Ⅲ支疼痛者或第Ⅰ、Ⅱ、Ⅲ支同时疼痛者应用Hartel前入路半月神经节射频热凝治疗,其中260例患者应用三叉神经卵圆孔定位仪辅助定位,对39例患者术中应用X线或三维CT进行卵圆孔靶点验证。结果所有病例穿刺成功。术后即刻疗效:优良206例,良好42例,无疗效12例,总有效率95.4%,无严重并发症发生。结论卵圆孔定位仪可用于射频热凝治疗三叉神经痛的辅助定位,可以提高穿刺的成功率和安全性。     

Hepatic Disposition Characteristics of Electrically Charged Macromolecules in Rat in Vivo and in the Perfused Liver

The effect of electric charge on the hepatic disposition of macromolecules was studied in the rat. Charged derivatives of dextran (T-70) and bovine serum albumin (BSA), mitomycin C–dextran conjugates (MMC-D), and lactosaminated BSA (Lac-BSA) were employed as model macromolecules. After intravenous injection, cationic macromolecules were rapidly eliminated from plasma because of their extensive hepatic uptake, while anionic and neutral macromolecules were slowly eliminated. Cationic macromolecules were recovered from parenchymal and nonparenchymal hepatic cells at a cellular uptake (per unit cell number) ratio of 1.4–3.2, while that of Lac-BSA was 14. During liver perfusion using a single-pass constant infusion mode, cationic macromolecules were continuously extracted by the liver, with extraction ratios at steady-state (E _ss) ranging between 0.03 and 0.54, whereas anionic and neutral macromolecules were almost completely recovered in the outflow at steady state. The E _ss for cationized BSA (Cat-BSA) and cationic MMC-Dcat were concentration dependent and decreased at low temperatures and in the presence of colchicine and cytochalasin B. The possible participation of the internalization process in the uptake of cationic macromolecules by hepatocytes was suggested.     

Localizing and photosensitizing mechanism by tetra(3-hydroxyphenyl)porphin in vivo on human malignant melanoma xenografts in athymic nude mice

Observations on time-dependent localization of tetra(3-hydroxyphenyl)porphin (3-THPP) in human malignant melanoma transplanted to athymic nude mice from 1 to 120 h after intraperitoneal (i.p.) 10 mg kg^–1 b.w. administration were made by means of fluorescence microscopy. Fluorescence was found on the membrane of the melanoma cells and in the cytoplasm with a peak fluorescence intensity at 24 h post-injection of 3-THPP. The growth of the tumour cells was obviously inhibited at an early stage after PCT. Morphological changes of the tumour at various intervals after treatment by PCT with 3-THPP were also observed. Diffuse degeneration of the tumour cells with swelling of mitochondria and endoplasmic reticulum, heterochromatin aggregation and margination, etc., and subsequently diffuse necrosis with little or no the background of tumorous vascular response were found at an early stage after PCT. On the other hand, it was also observed that the necrosis of the melanoma areas was caused as a consequence of tumorous vascular injury at a later stage after PCT. Thus, two tumoricidal processes caused by PCT with 3-THPP were seen: a direct phototoxic action on tumour cells at an early stage after PCT and an indirect effect secondary to tumorous vascular injury at a later period after PCT.     

房室折返性心动过速RP‘时距的特征及对旁道定位的意义

应用食管调搏，检测６４例旁道参与的房室折返性心速患者Ⅰ、Ⅱ、Ⅴ１和食管导联的室房时距、Ｐ＇ｖ，Ｐｅｔ时距。发现左侧ＡＰ者ＲＰ＇１较ＲＰ＇Ｖ１短（Ｐ＜０．０１），而右侧ＡＰ时较ＲＰ＇ｖ１长（Ｐ＜０．０１）。     

癫痫的外科治疗

本文报告40例癫痫病人采用手术治疗。30例作了CT检查、脑电图检查,6例作脑电地形图检查,对手术定位有较大帮助。术中用脑皮层电图监测,有效地提高了癲痫源灶的切除率,手术有效者34例(85.0%)。作者还应用了胼胝体切开术,从病灶切除的病理所见,癫痫的外科治疗应引起神经外科的重视。     

Real-time refinement of subthalamic nucleus targeting using Bayesian decision-making on the root mean square measure.

The subthalamic nucleus (STN) is a major target for treatment of advanced Parkinson's disease patients undergoing deep brain stimulation surgery. Microelectrode recording (MER) is used in many cases to identify the target nucleus. A real-time procedure for identifying the entry and exit points of the STN would improve the outcome of this targeting procedure. We used the normalized root mean square (NRMS) of a short (5 seconds) MER sampled signal and the estimated anatomical distance to target (EDT) as the basis for this procedure. Electrode tip location was defined intraoperatively by an expert neurophysiologist to be before, within, or after the STN. Data from 46 trajectories of 27 patients were used to calculate the Bayesian posterior probability of being in each of these locations, given RMS-EDT pair values. We tested our predictions on each trajectory using a bootstrapping technique, with the rest of the trajectories serving as a training set and found the error in predicting the STN entry to be (mean +/- SD) 0.18 +/- 0.84, and 0.50 +/- 0.59 mm for STN exit point, which yields a 0.30 +/- 0.28 mm deviation from the expert's target center. The simplicity and computational ease of RMS calculation, its spike sorting-independent nature and tolerance to electrode parameters of this Bayesian predictor, can lead directly to the development of a fully automated intraoperative physiological procedure for the refinement of imaging estimates of STN borders.     

The comparative evaluation of cellular localization of viral antigens with microscopic changes in the ileum of cattle infected with bovine viral diarrhea

The correlation between microscopic changes with cellular localization of viral antigens was studied in the ileum of 16 cases infected with bovine viral diarrhea virus (BVDV). Microscopic lesions in the ileum included multifocal erosive and ulcerative ileitis, severe congestion and hemorrhage, crypt dilation and mucus engorgement, epithelial debris and leukocytes, lymphoid depletion of Peyer’s patches, herniation of mucosal epithelium into depleted Peyer’s patches, and fibrinoid vasculitis of submucosal vessels. BVDV antigen was detected by immunohistochemistry in macrophages, dendritic cells, smooth muscle cells, endothelial cells, epithelial cells of crypts, and mucosal epithelium, together with other mononuclear cells including lymphocytes, plasma cells, fibroblasts, and intramural ganglial cells. No consistent correlation between the presence of BVDV antigen and vascular lesions in the ileum was identified. The intensity and distribution of the immunoperoxidase stain in the ileum was graded as highly positive (18.7%), moderately positive (56.3%), and mildly positive (25%). In conclusion, the pattern and density of distribution and localization of BVDV antigen in the ileum was not consistently correlated with the severity of microscopic lesions.